p53 and Apoptosis: Master Guardian and Executioner Part 2

Size: px
Start display at page:

Download "p53 and Apoptosis: Master Guardian and Executioner Part 2"

Transcription

1 p53 and Apoptosis: Master Guardian and Executioner Part 2

2 p14arf in human cells is a antagonist of Mdm2. The expression of ARF causes a rapid increase in p53 levels, so what would you suggest?.. The enemy of an enemy is a friend.. ARF can induce rapid increases in p53 levels because it kidnaps and inhibits p53 s destroyer, Mdm2. in normal, unstressed cells, Mdm2 must be allowed to perform its normal role of keeping p53 levels very low. In many human tumors, inactivation of the p16ink4a/p14arf locus by genetic mutation or epigenetic promoter methylation can be demonstrated

3 many of the human cancer cells that retain wild-type p53 gene copies have eliminated p53 function by inactivating their two copies of the gene encoding ARF

4 ARF and p53-mediated apoptosis protect against cancer by monitoring intracellular signaling Several ways to eliminate cells that carry too much E2F activity and, by implication, have lost proper prb control. Huge E2F1 activity drives expression of a number of genes encoding apoptotic proteins. ( caspases 3, 7, 8, and 9), pro-apoptotic Bcl-2 related proteins (Bim, Noxa, PUMA), Apaf-1, and p53 s cousin, p73). The p53-dependent apoptotic program is often triggered by elevated E2F activity. p14arf gene carries an E2F recognition sequence in its promoter. Might be a target only at conditions with high level of E2F

5

6 prb E2F ARF Mdm2 p53 apoptosis ARF function is eliminated by a variety of molecular strategies during tumor formation = mutation of the p53 gene. These discussions suggest that E2F-induced apoptosis functions solely as an anticancer mechanism designed to eliminate unwanted, pre-neoplastic cells. other major oncogenic signaling pathway can also contribute significantly to increased ARF expression and thus to p53 activation downstream of Ras.

7 Hyperactive signaling by Ras or its immediate downstream partners, Raf or B-Raf drives increased ARF expression and, acting via Erk/MAPK, the expression of p53. These cells have to either neutralize p53 function or confront rapid elimination by p53-dependent apoptosis. In a transgenic mouse model of lung adenocarcinoma development, signaling by Ras oncoprotein and its activated downstream effector, phosphorylated Erk/MAPK.

8 p53 functions as a transcription factor that halts cell cycle advance in response to DNA damage and attempts to aid in the repair process Transcription-activating powers of p53 depend on more than its ability to recognize and bind this sequence within a promoter and acetylation, glycosylation, phosphorylation, and ribosylation. This affects the ability of p53 to interact physically with other factors (ex. phosphorylation of p53 s N-terminal transactivation domain can increase its ability to bind the Taz2 domain of the p300 co-activator). P300 then contributes to transcriptional activation by acetylating nearby histones H3and H4 as well as p53 itself.

9 What is the level of Mdm2 in cancer cells with mutant p53? Similar when cancer cells infected with SV40 LT, then p53 will stay high. What a bout its half life will be

10

11 p53 suppresses cancer through transcriptional activation, by regulating diverse biological processes through transactivation of target genes.

12 p53 suppresses cancer through transcriptional activation, by regulating diverse biological processes through transactivation of target genes. P53 works vis p21cip1 which is able to inhibit two CDKs CDK2 and CDC2 that are active in the late G1, S, G2, and M phases of the cell cycle. if the chromosomal DNA of a cell should suffer some damage during the G1 phase of the cell cycle, p53 will become activated, both by rapid increases in its concentration and by post-translational modifications that enable it to function effectively as a transcription factor. p53 will then induce p21cip1 synthesis, and p21cip1, in turn, will halt further cell proliferation

13 But this is not every thing! DNA repair proteins are mobilized far more effectively in cells carrying wild-type p53 alleles than in those with mutant p53 alleles. DNA polymerase β, is more active in p53 cells. p21cip1 induced by p53 can engage the DNA polymerase machinery at the replication fork and halt its further advance down DNA template molecules. In the event that the DNA is successfully repaired, the signals that have protected p53 from destruction will disappear. p21cip1 mediates some, but not all, of the tumor-suppressing activities of p53.

14 p53 often ushers in the apoptotic death program In response to massive, essentially irreparable genomic damage p53 will trigger apoptosis.

15

16 p53 inactivation provides advantage to incipient cancer cells at a number of steps in tumor progression Bcl-2 blocks apoptosis, while p53 promotes it. Bad can be phosphorylated by Akt/PKB, which decreases Bad s ability to hold the mitochondrial channels in an open configuration; this explains some of the anti-apoptotic effect of the Akt/PKB kinase. Bax and Bak proteins congregate at the outer surface of the mitochondrion, where they participate, in ways that are still

17 Altogether, the human genome is known to encode twenty-four Bcl-2 related proteins; six of these are antiapoptotic, while the remaining eighteen are pro-apoptotic.

18 - Bim is regulated at the transcriptional level and post-translationally via phosphorylation by Erk, which results in its ubiquitylation and degradation. - Bid is liberated from its inhibitory domain by caspases which are activated by granzyme b

19 Cancer cells invent numerous ways to inactivate some or all of the apoptotic machinery Toward neoplasia cells face many stressors, all of them are dangerous! Anoxia, deregulation of the prb pathway, activation of oncogenes like myc and ras, and various forms of DNA damage. Therefore cancer cells inactivate apoptosis via several ways. The p53 gene is altered in almost half of all human cancer cell genomes. Some times p53 is mislocalized. In many, ARF is no longer expressed by deletion of the ARFencoding gene or by promoter methylation Most sarcomas overexpress Mdm2. Some cancer cells deploy a protein termed FLIP

20 Many melanoma cells exhibit methylation promoter of the APAF1 gene. The pro-apoptotic Bax gene is inactivated by mutation in more than half the colon cancers. BCL2 expression is found to be elevated in more than half of human tumors. Hyper activation of the PI3K Akt/PKB pathway. Once Akt/PKB becomes activated by the PIP3 that accumulates, it can phosphorylate and thereby inhibit pro- poptotic proteins such as Bad, caspase 9, and IκB, and at the same time phosphorylate and activate Mdm2, the key antagonist of p53 Expression activation of the NF-κB transcription factor and therfore IAP-1, IAP-2, XIAP, IEX-1L, TRAF-1, and TRAF-2, which serve to block both the intrinsic and extrinsic apoptotic programs.

21 In activation of apoptotic machinery in cancer cells

22 In activation of apoptotic machinery in cancer cells

23 In activation of apoptotic machinery in cancer cells

Apoptosis Oncogenes. Srbová Martina

Apoptosis Oncogenes. Srbová Martina Apoptosis Oncogenes Srbová Martina Cell Cycle Control point Cyclin B Cdk1 Cyclin D Cdk4 Cdk6 Cyclin A Cdk2 Cyclin E Cdk2 Cyclin-dependent kinase (Cdk) have to bind a cyclin to become active Regulation

More information

Molecular biology :- Cancer genetics lecture 11

Molecular biology :- Cancer genetics lecture 11 Molecular biology :- Cancer genetics lecture 11 -We have talked about 2 group of genes that is involved in cellular transformation : proto-oncogenes and tumour suppressor genes, and it isn t enough to

More information

Cell cycle, signaling to cell cycle, and molecular basis of oncogenesis

Cell cycle, signaling to cell cycle, and molecular basis of oncogenesis Cell cycle, signaling to cell cycle, and molecular basis of oncogenesis MUDr. Jiří Vachtenheim, CSc. CELL CYCLE - SUMMARY Basic terminology: Cyclins conserved proteins with homologous regions; their cellular

More information

BIO360 Fall 2013 Quiz 1

BIO360 Fall 2013 Quiz 1 BIO360 Fall 2013 Quiz 1 1. Examine the diagram below. There are two homologous copies of chromosome one and the allele of YFG carried on the light gray chromosome has undergone a loss-of-function mutation.

More information

A class of genes that normally suppress cell proliferation. p53 and Rb..ect. suppressor gene products can release cells. hyperproliferation.

A class of genes that normally suppress cell proliferation. p53 and Rb..ect. suppressor gene products can release cells. hyperproliferation. Tumor Suppressor Genes A class of genes that normally suppress cell proliferation. p53 and Rb..ect Mutations that inactivate the tumor suppressor gene products can release cells from growth suppression

More information

MOLECULAR BASIS OF ONCOGENESIS

MOLECULAR BASIS OF ONCOGENESIS MOLECULAR BASIS OF ONCOGENESIS MUDr. Jiří Vachtenheim, CSc. 1 Cell processes which result also in cell cycle effects. Differentiation. Differentiated cells are usually in the G0 phase of the cell cycle.

More information

CELL CYCLE MOLECULAR BASIS OF ONCOGENESIS

CELL CYCLE MOLECULAR BASIS OF ONCOGENESIS CELL CYCLE MOLECULAR BASIS OF ONCOGENESIS Summary of the regulation of cyclin/cdk complexes during celll cycle Cell cycle phase Cyclin-cdk complex inhibitor activation Substrate(s) G1 Cyclin D/cdk 4,6

More information

Cancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation

Cancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation Cancer The fundamental defect is unregulated cell division. Properties of Cancerous Cells Altered growth and proliferation Loss of growth factor dependence Loss of contact inhibition Immortalization Alterated

More information

BCHM3972 Human Molecular Cell Biology (Advanced) 2013 Course University of Sydney

BCHM3972 Human Molecular Cell Biology (Advanced) 2013 Course University of Sydney BCHM3972 Human Molecular Cell Biology (Advanced) 2013 Course University of Sydney Page 2: Immune Mechanisms & Molecular Biology of Host Defence (Prof Campbell) Page 45: Infection and Implications for Cell

More information

RAS Genes. The ras superfamily of genes encodes small GTP binding proteins that are responsible for the regulation of many cellular processes.

RAS Genes. The ras superfamily of genes encodes small GTP binding proteins that are responsible for the regulation of many cellular processes. ۱ RAS Genes The ras superfamily of genes encodes small GTP binding proteins that are responsible for the regulation of many cellular processes. Oncogenic ras genes in human cells include H ras, N ras,

More information

Lecture 14 - The cell cycle and cell death

Lecture 14 - The cell cycle and cell death 02.17.10 Lecture 14 - The cell cycle and cell death The cell cycle: cells duplicate their contents and divide The cell cycle may be divided into 4 phases The cell cycle triggers essential processes (DNA

More information

Introduction to Cancer Biology

Introduction to Cancer Biology Introduction to Cancer Biology Robin Hesketh Multiple choice questions (choose the one correct answer from the five choices) Which ONE of the following is a tumour suppressor? a. AKT b. APC c. BCL2 d.

More information

Deregulation of signal transduction and cell cycle in Cancer

Deregulation of signal transduction and cell cycle in Cancer Deregulation of signal transduction and cell cycle in Cancer Tuangporn Suthiphongchai, Ph.D. Department of Biochemistry Faculty of Science, Mahidol University Email: tuangporn.sut@mahidol.ac.th Room Pr324

More information

Cancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation

Cancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation Cancer The fundamental defect is unregulated cell division. Properties of Cancerous Cells Altered growth and proliferation Loss of growth factor dependence Loss of contact inhibition Immortalization Alterated

More information

Apoptotic Pathways in Mammals Dr. Douglas R. Green

Apoptotic Pathways in Mammals Dr. Douglas R. Green Apoptotic Pathways in Mammals Douglas R. Green 1 Apoptosis A form of cell death that is defined morphologically, and features a number of biochemical events Programmed cell death Cell death that occurs

More information

Multistep nature of cancer development. Cancer genes

Multistep nature of cancer development. Cancer genes Multistep nature of cancer development Phenotypic progression loss of control over cell growth/death (neoplasm) invasiveness (carcinoma) distal spread (metastatic tumor) Genetic progression multiple genetic

More information

Cancer Biology How a cell responds to DNA Damage

Cancer Biology How a cell responds to DNA Damage 1 Cancer Biology How a cell responds to DNA Damage Jann Sarkaria Department of Oncology Mayo Clinic 2 EDUCATIONAL GOALS How proteins can transmit signals to each other. The definition of a tumor suppressor

More information

TUMOR-SUPPRESSOR GENES. Molecular Oncology Michael Lea

TUMOR-SUPPRESSOR GENES. Molecular Oncology Michael Lea TUMOR-SUPPRESSOR GENES Molecular Oncology 2011 Michael Lea TUMOR-SUPPRESSOR GENES - Lecture Outline 1. Summary of tumor suppressor genes 2. P53 3. Rb 4. BRCA1 and 2 5. APC and DCC 6. PTEN and PPA2 7. LKB1

More information

Karyotype analysis reveals transloction of chromosome 22 to 9 in CML chronic myelogenous leukemia has fusion protein Bcr-Abl

Karyotype analysis reveals transloction of chromosome 22 to 9 in CML chronic myelogenous leukemia has fusion protein Bcr-Abl Chapt. 18 Cancer Molecular Biology of Cancer Student Learning Outcomes: Describe cancer diseases in which cells no longer respond Describe how cancers come from genomic mutations (inherited or somatic)

More information

BIO360 Fall 2013 Quiz 1

BIO360 Fall 2013 Quiz 1 BIO360 Fall 2013 Quiz 1 Name: Key 1. Examine the diagram below. There are two homologous copies of chromosome one and the allele of YFG carried on the light gray chromosome has undergone a loss-of-function

More information

Introduction to pathology lecture 5/ Cell injury apoptosis. Dr H Awad 2017/18

Introduction to pathology lecture 5/ Cell injury apoptosis. Dr H Awad 2017/18 Introduction to pathology lecture 5/ Cell injury apoptosis Dr H Awad 2017/18 Apoptosis = programmed cell death = cell suicide= individual cell death Apoptosis cell death induced by a tightly regulated

More information

Determination Differentiation. determinated precursor specialized cell

Determination Differentiation. determinated precursor specialized cell Biology of Cancer -Developmental Biology: Determination and Differentiation -Cell Cycle Regulation -Tumor genes: Proto-Oncogenes, Tumor supressor genes -Tumor-Progression -Example for Tumor-Progression:

More information

Cancer: Brief Introduction. First stage: Mutations in genes progressively accumulate so that there is unrestrained cell proliferation

Cancer: Brief Introduction. First stage: Mutations in genes progressively accumulate so that there is unrestrained cell proliferation Cancer: Brief Introduction First stage: Mutations in genes progressively accumulate so that there is unrestrained cell proliferation There has to be mutational amplification Over lifetime about 10 16 divisions

More information

Lecture 8 Neoplasia II. Dr. Nabila Hamdi MD, PhD

Lecture 8 Neoplasia II. Dr. Nabila Hamdi MD, PhD Lecture 8 Neoplasia II Dr. Nabila Hamdi MD, PhD ILOs Understand the definition of neoplasia. List the classification of neoplasia. Describe the general characters of benign tumors. Understand the nomenclature

More information

Mechanisms of Cell Death

Mechanisms of Cell Death Mechanisms of Cell Death CELL DEATH AND FORMATION OF THE SEMICIRCULAR CANALS Carol M. Troy August 25, 2008 FROM: Fekete et al., Development 124: 2451 (1997) PHENOMENOLOGY OF CELL DEATH I. DEVELOPMENT A.

More information

Tumor suppressor genes D R. S H O S S E I N I - A S L

Tumor suppressor genes D R. S H O S S E I N I - A S L Tumor suppressor genes 1 D R. S H O S S E I N I - A S L What is a Tumor Suppressor Gene? 2 A tumor suppressor gene is a type of cancer gene that is created by loss-of function mutations. In contrast to

More information

609G: Concepts of Cancer Genetics and Treatments (3 credits)

609G: Concepts of Cancer Genetics and Treatments (3 credits) Master of Chemical and Life Sciences Program College of Computer, Mathematical, and Natural Sciences 609G: Concepts of Cancer Genetics and Treatments (3 credits) Text books: Principles of Cancer Genetics,

More information

Emerging" hallmarks of cancer, a. Reprogramming of energy metabolism b. Evasion of the immune system, Enabling characteristics, a.

Emerging hallmarks of cancer, a. Reprogramming of energy metabolism b. Evasion of the immune system, Enabling characteristics, a. HALLMARKS OF CANCER - Together dictate the malignant phenotype. 1. Self-sufficiency in growth signals 2. Insensitivity to growth inhibitory signals 3. Evasion of cell death 4. Limitless replicative potential

More information

Oncogenes and tumour suppressor genes

Oncogenes and tumour suppressor genes Cancer mutations disrupt cellular homeostasis Oncogenes and tumour suppressor genes Oncogenes: Gain of function mutations Proto-oncogene Tumour suppressor genes: loss of function mutations Normal cell

More information

The functional investigation of the interaction between TATA-associated factor 3 (TAF3) and p53 protein

The functional investigation of the interaction between TATA-associated factor 3 (TAF3) and p53 protein THESIS BOOK The functional investigation of the interaction between TATA-associated factor 3 (TAF3) and p53 protein Orsolya Buzás-Bereczki Supervisors: Dr. Éva Bálint Dr. Imre Miklós Boros University of

More information

Apoptosis Chapter 9. Neelu Yadav PhD

Apoptosis Chapter 9. Neelu Yadav PhD Apoptosis Chapter 9 Neelu Yadav PhD Neelu.Yadav@Roswellpark.org 1 Apoptosis: Lecture outline Apoptosis a programmed cell death pathway in normal homeostasis Core Apoptosis cascade is conserved Compare

More information

Section D: The Molecular Biology of Cancer

Section D: The Molecular Biology of Cancer CHAPTER 19 THE ORGANIZATION AND CONTROL OF EUKARYOTIC GENOMES Section D: The Molecular Biology of Cancer 1. Cancer results from genetic changes that affect the cell cycle 2. Oncogene proteins and faulty

More information

Ch. 18 Regulation of Gene Expression

Ch. 18 Regulation of Gene Expression Ch. 18 Regulation of Gene Expression 1 Human genome has around 23,688 genes (Scientific American 2/2006) Essential Questions: How is transcription regulated? How are genes expressed? 2 Bacteria regulate

More information

Cancer. Throughout the life of an individual, but particularly during development, every cell constantly faces decisions.

Cancer. Throughout the life of an individual, but particularly during development, every cell constantly faces decisions. Cancer Throughout the life of an individual, but particularly during development, every cell constantly faces decisions. Should it divide? Yes No--> Should it differentiate? Yes No-->Should it die? Yes-->Apoptosis

More information

Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture:

Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture: Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture: Spandana Baruah December, 2016 Cancer is defined as: «A disease caused

More information

Oncogenes and Tumor Suppressors MCB 5068 November 12, 2013 Jason Weber

Oncogenes and Tumor Suppressors MCB 5068 November 12, 2013 Jason Weber Oncogenes and Tumor Suppressors MCB 5068 November 12, 2013 Jason Weber jweber@dom.wustl.edu Oncogenes & Cancer DNA Tumor Viruses Simian Virus 40 p300 prb p53 Large T Antigen Human Adenovirus p300 E1A

More information

Signaling Apoptosis. Scott André Oakes, M.D. Dept. of Pathology Univ. of Calif-San Francisco. Cyt c Release BAX/BAK. Apoptosome Formation

Signaling Apoptosis. Scott André Oakes, M.D. Dept. of Pathology Univ. of Calif-San Francisco. Cyt c Release BAX/BAK. Apoptosome Formation Signaling Apoptosis Cyt c Release BAX/BAK Apoptosome Formation Caspase Activation Scott André Oakes, M.D. Dept. of Pathology Univ. of Calif-San Francisco Why do we need cell death? Sculpt Organs Control

More information

Cell cycle and Apoptosis. Chalermchai Mitrpant

Cell cycle and Apoptosis. Chalermchai Mitrpant Cell cycle and Apoptosis 2556 Chalermchai Mitrpant Overview of the cell cycle Outline Regulatory mechanisms controlling cell cycle Progression of the cell cycle Checkpoint of the cell cycle Phases of the

More information

number Done by Corrected by Doctor Maha Shomaf

number Done by Corrected by Doctor Maha Shomaf number 19 Done by Waseem Abo-Obeida Corrected by Abdullah Zreiqat Doctor Maha Shomaf Carcinogenesis: the molecular basis of cancer. Non-lethal genetic damage lies at the heart of carcinogenesis and leads

More information

Part I Molecular Cell Biology

Part I Molecular Cell Biology 1 Part I Molecular Cell Biology RNA Regulation: Advances in Molecular Biology and Medicine, First Edition. Edited by Robert A. Meyers. 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH

More information

mirna Dr. S Hosseini-Asl

mirna Dr. S Hosseini-Asl mirna Dr. S Hosseini-Asl 1 2 MicroRNAs (mirnas) are small noncoding RNAs which enhance the cleavage or translational repression of specific mrna with recognition site(s) in the 3 - untranslated region

More information

TARGETS OF CYCLIN D1-CDK

TARGETS OF CYCLIN D1-CDK TARGETS OF CYCLIN D1-CDK FIRST TARGET OF THE COMPLEX CYCLIN D-KINASI: prb, IS THE PRODUCT OF THE GENE CONFERRING SUSCEPTIBILITY TO RETINOBLASTOMA - ABSENT OR MUTATED IN SEVERAL HUMAN CANCERS - TRANSCRIPTIONL

More information

Oncolytic virus strategy

Oncolytic virus strategy Oncolytic viruses Oncolytic virus strategy normal tumor NO replication replication survival lysis Oncolytic virus strategy Mechanisms of tumor selectivity of several, some of them naturally, oncolytic

More information

Cancer and Gene Alterations - 1

Cancer and Gene Alterations - 1 Cancer and Gene Alterations - 1 Cancer and Gene Alteration As we know, cancer is a disease of unregulated cell growth. Although we looked at some of the features of cancer when we discussed mitosis checkpoints,

More information

Problem Set 8 Key 1 of 8

Problem Set 8 Key 1 of 8 7.06 2003 Problem Set 8 Key 1 of 8 7.06 2003 Problem Set 8 Key 1. As a bright MD/PhD, you are interested in questions about the control of cell number in the body. Recently, you've seen three patients

More information

#19 Apoptosis Chapter 9. Neelu Yadav PhD

#19 Apoptosis Chapter 9. Neelu Yadav PhD #19 Apoptosis Chapter 9 Neelu Yadav PhD Neelu.Yadav@Roswellpark.org Why cells decide to die? - Stress, harmful, not needed - Completed its life span Death stimulation or Stress Cell Survival Death Functions

More information

Supplementary Figures

Supplementary Figures Supplementary Figures Figure S1. Validation of kinase regulators of ONC201 sensitivity. Validation and screen results for changes in cell viability associated with the combination of ONC201 treatment (1

More information

Molecular Cell Biology Spring 2014, Michael Pavlov To read: relevant parts from chapters 20 and 25.

Molecular Cell Biology Spring 2014, Michael Pavlov To read: relevant parts from chapters 20 and 25. Molecular Cell Biology Spring 2014, Michael Pavlov To read: relevant parts from chapters 20 and 25. Lecture 10: Initiation of the Cell Cycle and its aberrations. Cip/Kip and Ink4 brake the cell cycle Inhibition

More information

Table S1. New colony formation 7 days after stimulation with doxo and VCR in JURKAT cells

Table S1. New colony formation 7 days after stimulation with doxo and VCR in JURKAT cells Table S1. New colony formation 7 days after stimulation with and in JURKAT cells drug co + number of colonies 7±14 4±7 48±11 JURKAT cells were stimulated and analyzed as in Table 1. Drug concentrations

More information

Early Embryonic Development

Early Embryonic Development Early Embryonic Development Maternal effect gene products set the stage by controlling the expression of the first embryonic genes. 1. Transcription factors 2. Receptors 3. Regulatory proteins Maternal

More information

Signaling. Dr. Sujata Persad Katz Group Centre for Pharmacy & Health research

Signaling. Dr. Sujata Persad Katz Group Centre for Pharmacy & Health research Signaling Dr. Sujata Persad 3-020 Katz Group Centre for Pharmacy & Health research E-mail:sujata.persad@ualberta.ca 1 Growth Factor Receptors and Other Signaling Pathways What we will cover today: How

More information

CELL CYCLE REGULATION AND CANCER. Cellular Reproduction II

CELL CYCLE REGULATION AND CANCER. Cellular Reproduction II CELL CYCLE REGULATION AND CANCER Cellular Reproduction II THE CELL CYCLE Interphase G1- gap phase 1- cell grows and develops S- DNA synthesis phase- cell replicates each chromosome G2- gap phase 2- cell

More information

The Biology and Genetics of Cells and Organisms The Biology of Cancer

The Biology and Genetics of Cells and Organisms The Biology of Cancer The Biology and Genetics of Cells and Organisms The Biology of Cancer Mendel and Genetics How many distinct genes are present in the genomes of mammals? - 21,000 for human. - Genetic information is carried

More information

Cell Cycle Regulation. Adrian R. Black

Cell Cycle Regulation. Adrian R. Black Cell Cycle Regulation Adrian R. Black 845-3090 Adrian.black@roswellpark.org Loss of Growth Control Block of Apoptosis Evasion of Senescence Angiogenesis Invasion hases of the cell cycle Mitosis: Chromosome

More information

Cancer genetics

Cancer genetics Cancer genetics General information about tumorogenesis. Cancer induced by viruses. The role of somatic mutations in cancer production. Oncogenes and Tumor Suppressor Genes (TSG). Hereditary cancer. 1

More information

Regulation of Gene Expression in Eukaryotes

Regulation of Gene Expression in Eukaryotes Ch. 19 Regulation of Gene Expression in Eukaryotes BIOL 222 Differential Gene Expression in Eukaryotes Signal Cells in a multicellular eukaryotic organism genetically identical differential gene expression

More information

7.012 Problem Set 6 Solutions

7.012 Problem Set 6 Solutions Name Section 7.012 Problem Set 6 Solutions Question 1 The viral family Orthomyxoviridae contains the influenza A, B and C viruses. These viruses have a (-)ss RNA genome surrounded by a capsid composed

More information

Chapt 15: Molecular Genetics of Cell Cycle and Cancer

Chapt 15: Molecular Genetics of Cell Cycle and Cancer Chapt 15: Molecular Genetics of Cell Cycle and Cancer Student Learning Outcomes: Describe the cell cycle: steps taken by a cell to duplicate itself = cell division; Interphase (G1, S and G2), Mitosis.

More information

Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo, Induces Apoptosis in a T-Cell Leukemia Cell Line, Jurkat E6-1

Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo, Induces Apoptosis in a T-Cell Leukemia Cell Line, Jurkat E6-1 Mar. Drugs 2013, 11, 3224-3257; doi:10.3390/md11093224 Article OPEN ACCESS marine drugs ISSN 1660-3397 www.mdpi.com/journal/marinedrugs Epigonal Conditioned Media from Bonnethead Shark, Sphyrna tiburo,

More information

Prokaryotes and eukaryotes alter gene expression in response to their changing environment

Prokaryotes and eukaryotes alter gene expression in response to their changing environment Chapter 18 Prokaryotes and eukaryotes alter gene expression in response to their changing environment In multicellular eukaryotes, gene expression regulates development and is responsible for differences

More information

Genome of Hepatitis B Virus. VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department

Genome of Hepatitis B Virus. VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department Genome of Hepatitis B Virus VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department Proto Oncogen and Oncogen Oncogen Proteins that possess the ability to cause

More information

Prepared by Cyrus H. Nozad, MD, University of Tennessee and John Seyerle, MD, Ohio State University

Prepared by Cyrus H. Nozad, MD, University of Tennessee and John Seyerle, MD, Ohio State University Allergy and Immunology Review Corner: Chapter 21 of Middleton s Allergy Principles and Practice, Seventh Edition, edited by N. Franklin Adkinson, et al. Chapter 21: Antigen-Presenting Dendritic Cells (Pages

More information

VIII Curso Internacional del PIRRECV. Some molecular mechanisms of cancer

VIII Curso Internacional del PIRRECV. Some molecular mechanisms of cancer VIII Curso Internacional del PIRRECV Some molecular mechanisms of cancer Laboratorio de Comunicaciones Celulares, Centro FONDAP Estudios Moleculares de la Celula (CEMC), ICBM, Facultad de Medicina, Universidad

More information

#19 Apoptosis Chapter 9. Neelu Yadav PhD

#19 Apoptosis Chapter 9. Neelu Yadav PhD #19 Apoptosis Chapter 9 Neelu Yadav PhD Neelu.Yadav@Roswellpark.org Why cells decide to die? - Stress, harmful, not needed - Completed its life span Death stimulation or Stress Cell Survival Death Functions

More information

Computer Science, Biology, and Biomedical Informatics (CoSBBI) Outline. Molecular Biology of Cancer AND. Goals/Expectations. David Boone 7/1/2015

Computer Science, Biology, and Biomedical Informatics (CoSBBI) Outline. Molecular Biology of Cancer AND. Goals/Expectations. David Boone 7/1/2015 Goals/Expectations Computer Science, Biology, and Biomedical (CoSBBI) We want to excite you about the world of computer science, biology, and biomedical informatics. Experience what it is like to be a

More information

BIO360 Quiz #1. September 14, Name five of the six Hallmarks of Cancer (not emerging hallmarks or enabling characteristics ): (5 points)

BIO360 Quiz #1. September 14, Name five of the six Hallmarks of Cancer (not emerging hallmarks or enabling characteristics ): (5 points) Name: BIO360 Quiz #1 September 14, 2012 1. Name five of the six Hallmarks of Cancer (not emerging hallmarks or enabling characteristics ): (5 points) 2. The controversial hypothesis that only a small subset

More information

Overview: Conducting the Genetic Orchestra Prokaryotes and eukaryotes alter gene expression in response to their changing environment

Overview: Conducting the Genetic Orchestra Prokaryotes and eukaryotes alter gene expression in response to their changing environment Overview: Conducting the Genetic Orchestra Prokaryotes and eukaryotes alter gene expression in response to their changing environment In multicellular eukaryotes, gene expression regulates development

More information

The discovery of Bcl-2

The discovery of Bcl-2 The discovery of Bcl-2 Bcl-2: B-cell lymphoma 2 The pro-survival subfamily of Bcl-2 protein family Cloning of Bcl-2 as the oncogene which is deregulated at t(14;18) lymphomas Pioneer works by Tsujimoto

More information

Genomic instability. Amin Mahpour

Genomic instability. Amin Mahpour Genomic instability Amin Mahpour 1 Some questions to ponder What is Genomic instability? What factors contribute to the genomic integrity? How we identify these aberrations? 2 PART I: MOLECULAR BIOLOGY

More information

GMS 6644: Apoptosis. Introduction

GMS 6644: Apoptosis. Introduction GMS 6644: Apoptosis Introduction (Feb. 15, 2006) Lei Xiao, Ph.D. Department of Anatomy & Cell Biology UF Shands Cancer Center ARB Rm R4-250, 846-1199, lxiao@ufl.edu Outline of the Lecture Different types

More information

Characterization of N-terminal Myc ubiquitylation and the novel oncogene CUL7

Characterization of N-terminal Myc ubiquitylation and the novel oncogene CUL7 Characterization of N-terminal Myc ubiquitylation and the novel oncogene CUL7 by Sam Sulgi Kim A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of

More information

Intrinsic cellular defenses against virus infection

Intrinsic cellular defenses against virus infection Intrinsic cellular defenses against virus infection Detection of virus infection Host cell response to virus infection Interferons: structure and synthesis Induction of antiviral activity Viral defenses

More information

CELL BIOLOGY - CLUTCH CH CANCER.

CELL BIOLOGY - CLUTCH CH CANCER. !! www.clutchprep.com CONCEPT: OVERVIEW OF CANCER Cancer is a disease which is primarily caused from misregulated cell division, which form There are two types of tumors - Benign tumors remain confined

More information

Polyomaviridae. Spring

Polyomaviridae. Spring Polyomaviridae Spring 2002 331 Antibody Prevalence for BK & JC Viruses Spring 2002 332 Polyoma Viruses General characteristics Papovaviridae: PA - papilloma; PO - polyoma; VA - vacuolating agent a. 45nm

More information

Pancreatic Cancer Research and HMGB1 Signaling Pathway

Pancreatic Cancer Research and HMGB1 Signaling Pathway Pancreatic Cancer Research and HMGB1 Signaling Pathway Haijun Gong*, Paolo Zuliani*, Anvesh Komuravelli*, James R. Faeder #, Edmund M. Clarke* * # The Hallmarks of Cancer D. Hanahan and R. A. Weinberg

More information

Part-4. Cell cycle regulatory protein 5 (Cdk5) A novel target of ERK in Carb induced cell death

Part-4. Cell cycle regulatory protein 5 (Cdk5) A novel target of ERK in Carb induced cell death Part-4 Cell cycle regulatory protein 5 (Cdk5) A novel target of ERK in Carb induced cell death 95 1. Introduction The process of replicating DNA and dividing cells can be described as a series of coordinated

More information

Oncogenes and Tumor. supressors

Oncogenes and Tumor. supressors Oncogenes and Tumor supressors From history to therapeutics Serge ROCHE Neoplastic transformation TUMOR SURESSOR ONCOGENE ONCOGENES History 1911 1960 1980 2001 Transforming retrovirus RSV v-src is an oncogene

More information

Introduction. Cancer Biology. Tumor-suppressor genes. Proto-oncogenes. DNA stability genes. Mechanisms of carcinogenesis.

Introduction. Cancer Biology. Tumor-suppressor genes. Proto-oncogenes. DNA stability genes. Mechanisms of carcinogenesis. Cancer Biology Chapter 18 Eric J. Hall., Amato Giaccia, Radiobiology for the Radiologist Introduction Tissue homeostasis depends on the regulated cell division and self-elimination (programmed cell death)

More information

Regarding techniques of proteomics, there is:

Regarding techniques of proteomics, there is: Molecular الحلقة biology 14 واألخيرة To put you back in the context; the discussion was about Trancriptomics (the study of transcription). The following topic will be PROTEOMICS, which is the study of

More information

CANCER. Inherited Cancer Syndromes. Affects 25% of US population. Kills 19% of US population (2nd largest killer after heart disease)

CANCER. Inherited Cancer Syndromes. Affects 25% of US population. Kills 19% of US population (2nd largest killer after heart disease) CANCER Affects 25% of US population Kills 19% of US population (2nd largest killer after heart disease) NOT one disease but 200-300 different defects Etiologic Factors In Cancer: Relative contributions

More information

Apoptotic cell signaling in cancer progression and therapyw

Apoptotic cell signaling in cancer progression and therapyw Integrative Biology Dynamic Article Links Cite this: Integr. Biol., 2011, 3, 279 296 www.rsc.org/ibiology REVIEW ARTICLE Apoptotic cell signaling in cancer progression and therapyw Jessica Plati, a Octavian

More information

Early cell death (FGF) B No RunX transcription factor produced Yes No differentiation

Early cell death (FGF) B No RunX transcription factor produced Yes No differentiation Solution Key - Practice Questions Question 1 a) A recent publication has shown that the fat stem cells (FSC) can act as bone stem cells to repair cavities in the skull, when transplanted into immuno-compromised

More information

Prof. R. V. Skibbens

Prof. R. V. Skibbens Prof. R. V. Skibbens December 2, 2011 BIOS 10: BioScience in the 21 st Century Cell Cycle, Cell Division and Cancer (Part 2) Directionality The Cell Cycle clock goes in only one direction S-phase cells

More information

Studies of mutant p53-targeting small molecules

Studies of mutant p53-targeting small molecules Department of Oncology-Pathology Cancer Center Karolinska Karolinska Institutet, Stockholm, Sweden Studies of mutant p53-targeting small molecules Nicole Zache Stockholm 2007 Supervisor: Professor Klas

More information

Activation of cellular proto-oncogenes to oncogenes. How was active Ras identified?

Activation of cellular proto-oncogenes to oncogenes. How was active Ras identified? Dominant Acting Oncogenes Eugene E. Marcantonio, M.D. Ph.D. Oncogenes are altered forms of normal cellular genes called proto-oncogenes that are involved in pathways regulating cell growth, differentiation,

More information

Regulation of Cell Division (Ch. 12)

Regulation of Cell Division (Ch. 12) Regulation of Cell Division (Ch. 12) Coordination of cell division A multicellular organism needs to coordinate cell division across different tissues & organs critical for normal growth, development &

More information

Regulation of cell cycle. Dr. SARRAY Sameh, Ph.D

Regulation of cell cycle. Dr. SARRAY Sameh, Ph.D Regulation of cell cycle Dr. SARRAY Sameh, Ph.D Control of cell cycle: Checkpoints Are the cell cycle controls mechanisms in eukaryotic cells. These checkpoints verify whether the processes at each phase

More information

Basic tumor nomenclature

Basic tumor nomenclature Jonas Nilsson jonas.a.nilsson@surgery.gu.se Sahlgrenska Cancer Center Bilder gjorda av Per Holmfeldt och Jonas Nilsson Benign tumor Basic tumor nomenclature Malignant tumor = cancer Metastasis Carcinoma:

More information

Enzyme-coupled Receptors. Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors

Enzyme-coupled Receptors. Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors Enzyme-coupled Receptors Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors Cell-surface receptors allow a flow of ions across the plasma

More information

Cell Cycle and Cancer

Cell Cycle and Cancer 142 8. Cell Cycle and Cancer NOTES CELL CYCLE G 0 state o Resting cells may re-enter the cell cycle Nondividing cells (skeletal and cardiac muscle, neurons) o Have left the cell cycle and cannot undergo

More information

Programmed Cell Death (apoptosis)

Programmed Cell Death (apoptosis) Programmed Cell Death (apoptosis) Stereotypic death process includes: membrane blebbing nuclear fragmentation chromatin condensation and DNA framentation loss of mitochondrial integrity and release of

More information

Disorders of Cell Growth & Neoplasia. Lecture 4 Molecular basis of cancer

Disorders of Cell Growth & Neoplasia. Lecture 4 Molecular basis of cancer General Pathology VPM 152 Disorders of Cell Growth & Neoplasia Lecture 4 Molecular basis of cancer Enrique Aburto Apr 2010 Skin tumor in a 10-year-old Rottweiler. Considering the external appearance and

More information

oncogenes-and- tumour-suppressor-genes)

oncogenes-and- tumour-suppressor-genes) Special topics in tumor biochemistry oncogenes-and- tumour-suppressor-genes) Speaker: Prof. Jiunn-Jye Chuu E-Mail: jjchuu@mail.stust.edu.tw Genetic Basis of Cancer Cancer-causing mutations Disease of aging

More information

Lecture 10. G1/S Regulation and Cell Cycle Checkpoints. G1/S regulation and growth control G2 repair checkpoint Spindle assembly or mitotic checkpoint

Lecture 10. G1/S Regulation and Cell Cycle Checkpoints. G1/S regulation and growth control G2 repair checkpoint Spindle assembly or mitotic checkpoint Lecture 10 G1/S Regulation and Cell Cycle Checkpoints Outline: G1/S regulation and growth control G2 repair checkpoint Spindle assembly or mitotic checkpoint Paper: The roles of Fzy/Cdc20 and Fzr/Cdh1

More information

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.

Follicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development. Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy

More information

Eukaryotic Gene Regulation

Eukaryotic Gene Regulation Eukaryotic Gene Regulation Chapter 19: Control of Eukaryotic Genome The BIG Questions How are genes turned on & off in eukaryotes? How do cells with the same genes differentiate to perform completely different,

More information

Negative Regulation of c-myc Oncogenic Activity Through the Tumor Suppressor PP2A-B56α

Negative Regulation of c-myc Oncogenic Activity Through the Tumor Suppressor PP2A-B56α Negative Regulation of c-myc Oncogenic Activity Through the Tumor Suppressor PP2A-B56α Mahnaz Janghorban, PhD Dr. Rosalie Sears lab 2/8/2015 Zanjan University Content 1. Background (keywords: c-myc, PP2A,

More information

A Genetic Program for Embryonic Development

A Genetic Program for Embryonic Development Concept 18.4: A program of differential gene expression leads to the different cell types in a multicellular organism During embryonic development, a fertilized egg gives rise to many different cell types

More information

Review Article. p53 AND CANCER

Review Article. p53 AND CANCER Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2016, 8(6):112-118 Review Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 p53 AND CANCER Momina S. Alvi 1, Ismat Fatima Rizvi²,

More information

Rino Ragno Rome Center for Molecular Design Department of Chemistry and Phamaceutical Technology Faculty of Pharmacy and Medicine

Rino Ragno Rome Center for Molecular Design Department of Chemistry and Phamaceutical Technology Faculty of Pharmacy and Medicine Rino Ragno Rome Center for Molecular Design Department of Chemistry and Phamaceutical Technology Faculty of Pharmacy and Medicine HDAC Inhibitors: Structure-Based Modeling and Isoform-Selectivity Prediction

More information