HPV-16 protein interactions. Ramya M Gundurao, Heather A Cubie, Jürgen Haas

Size: px
Start display at page:

Download "HPV-16 protein interactions. Ramya M Gundurao, Heather A Cubie, Jürgen Haas"

Transcription

1 HPV-16 protein interactions Ramya M Gundurao, Heather A Cubie, Jürgen Haas

2 HPV lifecycle Woodman et al. Nature Reviews Cancer 7, (January 2007)

3 HPV lifecycle Woodman et al. Nature Reviews Cancer 7, (January 2007)

4 HPV lifecycle Woodman et al. Nature Reviews Cancer 7, (January 2007)

5 E7 Interactions: (Moody & Laimins, 2010)

6 RB E2F pathway RB E2F Cell cycle arrest CDK PP1c P P P P RB E2F Cell cycle progression

7 Aims To identify using yeast two-hybrid genomewide HPV protein interactions novel host binding partners of HPV

8 Yeast two-hybrid screen no protein interaction Prey Bait DBD X Y AD No transcription Preys Mating plate Diploid selection plate Interaction detection plates UAS REPORTER positive protein interaction X DBD Y AD Active transcription Baits UAS REPORTER X & Y proteins tested for interaction DBD - DNA binding domain AD - DNA activation domain UAS unique activation site

9 Results Genomewide screen Virus host screen

10 Intra-viral Screen Yeast two-hybrid screen Baits Preys Interaction detected and validated between E7 and E1(full length and N terminal 92 amino acids)

11 E1-E7 interaction mapping Myc tagged E7 deletion mutants CR1 CR2 CR3 E7 E7f4 E7f5 E7f6 E7f7 E7f8 normalised flurescence readout Interacting pair E1 interaction domain mapped to aa of E7

12 E7 site directed mutants 50HYNIVTFCCKC62 H51A Y52A N53A I54A V55A C59A C58A F57A T56A C61A K60A Normlised fluorescence readout Myc E EB Max E1 E1 E1 E1 E1 E1 E1 E1 E1 E1 E1 E1 EP Interacting pair E7 prb interaction CCKC (58-61aa) necessary for E1-E7 interaction In particular C58 and C61

13 HPV replication assay HPV replication assay 6 Fold change to pori M+E1+E water pori M only pori M + E1 pori M + E1 pori M + E1 pori M + E1 pori M + E1 pori M + E1 + E2 + E2 + E7 - + E2 + E7 + E2 + E7 + E2 + E7 1 ng C58A -1 ng C59A-1 ng C61A-1 ng Tranfected genes E7 downregulates HPV replication by 50% whereas E7 mutants unable to bind E1 do not inhibit replication in collaboration with Morgan Lab, Glasgow

14 Conclusions (1) HPV-16 E1 and E7 proteins interact N terminal 92 amino acids of E1 and zinc binding CCKC domain of E7 are necessary for interaction E7 might play an inhibitory role on E1 mediated HPV episomal replication

15 Genomewide screen Virus host screen

16 Virus host screen HPV proteins tested against human testis epithelial cell library 43 interactions identified for HPV proteins with cellular proteins

17 Virus host screen

18 LUMIER assay Normalised signal to background ratio FOS HPV-16 E7 HPV-16 E1^E2C HPV-16 L1 HPV 16 E1^E4* HPV 16 E6*E7* HPV-18 E1 JUN SPZ1 RPL36AL ADORA3 EEF1a1 KIFC3 SLC25A46 Interacting partners 6 out of 21 interactions tested were positive

19 SPZ1 Spermatogenic leucine zipper protein originally discovered in mouse testis (Hsu et al, 2001) member of Helix loop Helix zipper proteins increases cell proliferation and tumourigenesis by MAPK pathway Upregulates of Proliferative cell nuclear antigen PCNA (Hsu et al, 2005) interacts with protein phosphatase PP1cy2 and reduces its phosphorylase activity (Hrabchek & Vermuza,2004) PP1c dephosphorylates RB (Vietri et al, 2006) Does SPZ1 play a role in E7 mediated tumourigenesis?

20 SPZ1 expression in cervical cancer cell lines

21 SPZ1 binding domain on E7 E7 CR1 CR2 CR3 CR2 (15-37 amino acids) necessary for E7 interaction with SPZ1 which is also Rb interaction domain

22 Interaction network of SPZ1 PP1cγ SPZ1 PP1cα E7 Rb Published interactions Novel interactions

23 SPZ1 stabilises RB

24 Current Work Does SPZ1 block dephosphorylation of RB by PP1c? Does E7 reduce PP1c phosphorylase activity? Does E7 enhance PCNA upregulation by SPZ1? Do E7 from other HPV types interact with SPZ1? Is SPZ1 overexpressed in cervical cancer patients? Understanding the role of SPZ1 in cervical carcinogenesis

25 Acknowledgements Division of pathway medicine University of Edinburgh Jürgen Haas Annette Murr Members of Haas Group Scottish HPV reference lab Edinburgh Heather Cubie Kate Cushieri Maurice Canham Max-von-Pettenkofer Institute Ludwig-Maximilians University, Munich Susanne Bailer Marcus Heinzemann Morgan Lab, University of Glasgow Iain Morgan Mary Donaldson College of Medicine and Veterinary Medicine

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

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

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

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

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

Name Section Problem Set 6

Name Section Problem Set 6 Name Section 7.012 Problem Set 6 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 of lipids

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

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

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

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

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

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

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

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

基醫所. The Cell Cycle. Chi-Wu Chiang, Ph.D. IMM, NCKU

基醫所. The Cell Cycle. Chi-Wu Chiang, Ph.D. IMM, NCKU 基醫所 The Cell Cycle Chi-Wu Chiang, Ph.D. IMM, NCKU 1 1 Introduction to cell cycle and cell cycle checkpoints 2 2 Cell cycle A cell reproduces by performing an orderly sequence of events in which it duplicates

More information

Regulators of Cell Cycle Progression

Regulators of Cell Cycle Progression Regulators of Cell Cycle Progression Studies of Cdk s and cyclins in genetically modified mice reveal a high level of plasticity, allowing different cyclins and Cdk s to compensate for the loss of one

More information

Supplemental Data Macrophage Migration Inhibitory Factor MIF Interferes with the Rb-E2F Pathway

Supplemental Data Macrophage Migration Inhibitory Factor MIF Interferes with the Rb-E2F Pathway Supplemental Data Macrophage Migration Inhibitory Factor MIF Interferes with the Rb-E2F Pathway S1 Oleksi Petrenko and Ute M. Moll Figure S1. MIF-Deficient Cells Have Reduced Transforming Ability (A) Soft

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

L I F E S C I E N C E S

L I F E S C I E N C E S 1a L I F E S C I E N C E S 5 -UUA AUA UUC GAA AGC UGC AUC GAA AAC UGU GAA UCA-3 5 -TTA ATA TTC GAA AGC TGC ATC GAA AAC TGT GAA TCA-3 3 -AAT TAT AAG CTT TCG ACG TAG CTT TTG ACA CTT AGT-5 OCTOBER 31, 2006

More information

Genetics and Cancer Ch 20

Genetics and Cancer Ch 20 Genetics and Cancer Ch 20 Cancer is genetic Hereditary cancers Predisposition genes Ex. some forms of colon cancer Sporadic cancers ~90% of cancers Descendants of cancerous cells all cancerous (clonal)

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

Problem Set 5 KEY

Problem Set 5 KEY 2006 7.012 Problem Set 5 KEY ** Due before 5 PM on THURSDAY, November 9, 2006. ** Turn answers in to the box outside of 68-120. PLEASE WRITE YOUR ANSWERS ON THIS PRINTOUT. 1. You are studying the development

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

VIRUSES AND CANCER Michael Lea

VIRUSES AND CANCER Michael Lea VIRUSES AND CANCER 2010 Michael Lea VIRAL ONCOLOGY - LECTURE OUTLINE 1. Historical Review 2. Viruses Associated with Cancer 3. RNA Tumor Viruses 4. DNA Tumor Viruses HISTORICAL REVIEW Historical Review

More information

BIOL 4374/BCHS 4313 Cell Biology Exam #1 February 13, 2001

BIOL 4374/BCHS 4313 Cell Biology Exam #1 February 13, 2001 BIOL 4374/BCHS 4313 Cell Biology Exam #1 February 13, 2001 SS# Name This exam is worth a total of 100 points. The number of points each question is worth is shown in parentheses. Good luck! 1. (2) The

More information

Molecular Cell Biology - Problem Drill 10: Gene Expression in Eukaryotes

Molecular Cell Biology - Problem Drill 10: Gene Expression in Eukaryotes Molecular Cell Biology - Problem Drill 10: Gene Expression in Eukaryotes Question No. 1 of 10 1. Which of the following statements about gene expression control in eukaryotes is correct? Question #1 (A)

More information

BL 424 Test pts name Multiple choice have one choice each and are worth 3 points.

BL 424 Test pts name Multiple choice have one choice each and are worth 3 points. BL 424 Test 3 2010 150 pts name Multiple choice have one choice each and are worth 3 points. 1. The plasma membrane functions as a a. selective barrier to the passage of molecules. b. sensor through which

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

1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples. Major Principles:

1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples. Major Principles: Carcinogenesis 1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples Carcinogenesis Major Principles: 1. Nonlethal genetic damage is central to

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

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

p53 and Apoptosis: Master Guardian and Executioner Part 2

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

More information

Interaction of NPR1 with basic leucine zipper protein transcription factors that bind sequences required for salicylic acid induction of the PR-1 gene

Interaction of NPR1 with basic leucine zipper protein transcription factors that bind sequences required for salicylic acid induction of the PR-1 gene Interaction of NPR1 with basic leucine zipper protein transcription factors that bind sequences required for salicylic acid induction of the PR-1 gene YUELIN ZHANG, WEIHUA FAN, MARK KINKEMA, XIN LI, AND

More information

HPV and Lower Genital Tract Disease. Simon Herrington University of Edinburgh, UK Royal Infirmary of Edinburgh, UK

HPV and Lower Genital Tract Disease. Simon Herrington University of Edinburgh, UK Royal Infirmary of Edinburgh, UK HPV and Lower Genital Tract Disease Simon Herrington University of Edinburgh, UK Royal Infirmary of Edinburgh, UK Conflict of interest/funding X None Company: Product royalties Paid consultant Research

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

7.012 Quiz 3 Answers

7.012 Quiz 3 Answers MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Friday 11/12/04 7.012 Quiz 3 Answers A > 85 B 72-84

More information

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

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

Institute of Radiation Biology. Oncogenes and tumour suppressor genes DoReMi Course 2014

Institute of Radiation Biology. Oncogenes and tumour suppressor genes DoReMi Course 2014 Institute of Radiation Biology Oncogenes and tumour suppressor genes DoReMi Course 2014 Hippocrates: Cause is systemic excess of black humor. Paracelsus challenges the humor theory. Suggests external

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

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

Alpha thalassemia mental retardation X-linked. Acquired alpha-thalassemia myelodysplastic syndrome

Alpha thalassemia mental retardation X-linked. Acquired alpha-thalassemia myelodysplastic syndrome Alpha thalassemia mental retardation X-linked Acquired alpha-thalassemia myelodysplastic syndrome (Alpha thalassemia mental retardation X-linked) Acquired alpha-thalassemia myelodysplastic syndrome Schematic

More information

Prof. R. V. Skibbens. Cell Cycle, Cell Division and Cancer (Part 2)

Prof. R. V. Skibbens. Cell Cycle, Cell Division and Cancer (Part 2) Prof. R. V. Skibbens November 22, 2010 BIOS 10: BioScience in the 21 st Century Cell Cycle, Cell Division and Cancer (Part 2) Directionality - clocks go in only one direction G1 doesn t have replication-inducing

More information

EMBO REPORT SUPPLEMENTARY SECTION. Quantitation of mitotic cells after perturbation of Notch signalling.

EMBO REPORT SUPPLEMENTARY SECTION. Quantitation of mitotic cells after perturbation of Notch signalling. EMBO REPORT SUPPLEMENTARY SECTION Quantitation of mitotic cells after perturbation of Notch signalling. Notch activation suppresses the cell cycle indistinguishably both within and outside the neural plate

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

Section 6. Junaid Malek, M.D.

Section 6. Junaid Malek, M.D. Section 6 Junaid Malek, M.D. The Golgi and gp160 gp160 transported from ER to the Golgi in coated vesicles These coated vesicles fuse to the cis portion of the Golgi and deposit their cargo in the cisternae

More information

for Microbiology Quality Assessment Programmes for HPV and MRSA Effect of change to assessment categories for HBV DNA Dr Vivienne James SoGAT 2009

for Microbiology Quality Assessment Programmes for HPV and MRSA Effect of change to assessment categories for HBV DNA Dr Vivienne James SoGAT 2009 for Microbiology Quality Assessment Programmes for HPV and MRSA Effect of change to assessment categories for HBV DNA Dr Vivienne James Overview Update on the HPV scheme introduced in 2009 MRSA screening

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

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

Lecture 7: Signaling Through Lymphocyte Receptors

Lecture 7: Signaling Through Lymphocyte Receptors Lecture 7: Signaling Through Lymphocyte Receptors Questions to Consider After recognition of its cognate MHC:peptide, how does the T cell receptor activate immune response genes? What are the structural

More information

Carcinogenesis. Carcinogenesis. 1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples

Carcinogenesis. Carcinogenesis. 1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples Carcinogenesis 1. Basic principles 2. 6 hallmark features 3. Abnormal cell proliferation: mechanisms 4. Carcinogens: examples Major Principles (cont d) 4. Principle targets of genetic damage: 4 classes

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

Materials and Methods , The two-hybrid principle.

Materials and Methods , The two-hybrid principle. The enzymatic activity of an unknown protein which cleaves the phosphodiester bond between the tyrosine residue of a viral protein and the 5 terminus of the picornavirus RNA Introduction Every day there

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

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

SSN SBPM Workshop Exam One. Short Answer Questions & Answers

SSN SBPM Workshop Exam One. Short Answer Questions & Answers SSN SBPM Workshop Exam One Short Answer Questions & Answers 1. Describe the effects of DNA damage on the cell cycle. ANS : DNA damage causes cell cycle arrest at a G2 checkpoint. This arrest allows time

More information

Proteasomes. When Death Comes a Knock n. Warren Gallagher Chem412, Spring 2001

Proteasomes. When Death Comes a Knock n. Warren Gallagher Chem412, Spring 2001 Proteasomes When Death Comes a Knock n Warren Gallagher Chem412, Spring 2001 I. Introduction Introduction The central dogma Genetic information is used to make proteins. DNA RNA Proteins Proteins are the

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

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

BioSci 145A Lecture 15 - Oncogenes and Cancer

BioSci 145A Lecture 15 - Oncogenes and Cancer BioSci 145A Lecture 15 - Oncogenes and Cancer Topics we will cover today Introduction to normal and cancer cells Characteristics of cells in culture Cancerous changes in cells Viruses can harbor transforming

More information

ARV Mode of Action. Mode of Action. Mode of Action NRTI. Immunopaedia.org.za

ARV Mode of Action. Mode of Action. Mode of Action NRTI. Immunopaedia.org.za ARV Mode of Action Mode of Action Mode of Action - NRTI Mode of Action - NNRTI Mode of Action - Protease Inhibitors Mode of Action - Integrase inhibitor Mode of Action - Entry Inhibitors Mode of Action

More information

Predictive PP1Ca binding region in BIG3 : 1,228 1,232aa (-KAVSF-) HEK293T cells *** *** *** KPL-3C cells - E E2 treatment time (h)

Predictive PP1Ca binding region in BIG3 : 1,228 1,232aa (-KAVSF-) HEK293T cells *** *** *** KPL-3C cells - E E2 treatment time (h) Relative expression ERE-luciferase activity activity (pmole/min) activity (pmole/min) activity (pmole/min) activity (pmole/min) MCF-7 KPL-3C ZR--1 BT-474 T47D HCC15 KPL-1 HBC4 activity (pmole/min) a d

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

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

Transcriptional regulation in Ebola Virus. The role of VP30

Transcriptional regulation in Ebola Virus. The role of VP30 Transcriptional regulation in Ebola Virus The role of VP30 Ebola virus www.ibtimes.com/updated-ebola-outbreak-map-virus-spreads-out-africa-death-toll-tops-4000-1703162 (2018/01/26) First symptoms 2 days

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

supplementary information

supplementary information DOI: 10.1038/ncb1875 Figure S1 (a) The 79 surgical specimens from NSCLC patients were analysed by immunohistochemistry with an anti-p53 antibody and control serum (data not shown). The normal bronchi served

More information

What are the implications of HPV in the biology of Head and Neck Cancer?

What are the implications of HPV in the biology of Head and Neck Cancer? What are the implications of HPV in the biology of Head and Neck Cancer? Raquel Ajub Moyses Friday, August 2nd, 2013 Disclosure Raquel Ajub Moyses has no significant financial relationship with any commercial

More information

otherwise known as Cytotoxic T lymphocytes (CTLs)

otherwise known as Cytotoxic T lymphocytes (CTLs) MIT Biology Department 7.012: Introductory Biology - Fall 200 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel NAME TA SEC 7.012 Problem Set 5 FRIDAY October 29, 2004

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

Invited Re vie W. Molecular genetics of ovarian carcinomas. Histology and Histo pathology

Invited Re vie W. Molecular genetics of ovarian carcinomas. Histology and Histo pathology Histol Histopathol (1 999) 14: 269-277 http://www.ehu.es/histol-histopathol Histology and Histo pathology Invited Re vie W Molecular genetics of ovarian carcinomas J. Diebold Pathological Institute, Ludwig-Maximilians-University

More information

Cellular Signaling Pathways. Signaling Overview

Cellular Signaling Pathways. Signaling Overview Cellular Signaling Pathways Signaling Overview Signaling steps Synthesis and release of signaling molecules (ligands) by the signaling cell. Transport of the signal to the target cell Detection of the

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

Nature Medicine: doi: /nm.4322

Nature Medicine: doi: /nm.4322 1 2 3 4 5 6 7 8 9 10 11 Supplementary Figure 1. Predicted RNA structure of 3 UTR and sequence alignment of deleted nucleotides. (a) Predicted RNA secondary structure of ZIKV 3 UTR. The stem-loop structure

More information

Supplementary Information

Supplementary Information Supplementary Information mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated carcinogenesis Zhang et al. a b d e g h Rel. Luc. Act. Rel. mrna Rel. mrna

More information

Role of Alpha-lipoic acid(ala) and statin in vascular smooth muscle cell proliferation

Role of Alpha-lipoic acid(ala) and statin in vascular smooth muscle cell proliferation Role of Alpha-lipoic acid(ala) and statin in vascular smooth muscle cell proliferation In-kyu Lee, M.D., Ph. D. Dept. of Internal Med, Keimyung Univ., School of Med. Taegu, Korea Oxidative Stress and Atherosclerosis

More information

MITOCW S05-L29

MITOCW S05-L29 MITOCW 7.013-S05-L29 And he took what was left, which much be very, very small, smaller than the size of a cell because the cells were removed by filtration, and he injected it into another bird. Now,

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 the Cell Cycle

Regulation of the Cell Cycle Regulation of the Cell Cycle 21 I. OVERVIEW Quiescent differentiated cell / can be induced to re-enter the active cell cycle. urvival Cell division Apoptosis 1 Daughter cells Apoptic cell enescent cell

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

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

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

Prof. R. V. Skibbens

Prof. R. V. Skibbens Prof. R. V. Skibbens September 8, 2017 BioScience in the 21 st Century Cell Cycle, Cell Division and intro to Cancer Cell growth and division What are the goals? I Cell Cycle what is this? response to

More information

Table of Contents. 1. Overview. 2. Interpretation Guide. 3. Staining Gallery Cases Negative for CINtec PLUS

Table of Contents. 1. Overview. 2. Interpretation Guide. 3. Staining Gallery Cases Negative for CINtec PLUS Staining Atlas Table of Contents 1. Overview 1.1 Introduction 1.2 Role of p16 INK4a 1.3 Role of Ki-67 1.4 Molecular Pathogenesis 1.5 p16 INK4a Expression in Cervical Dysplasia 1.6 The Concept of CINtec

More information

Cancer Genetics. What is Cancer? Cancer Classification. Medical Genetics. Uncontrolled growth of cells. Not all tumors are cancerous

Cancer Genetics. What is Cancer? Cancer Classification. Medical Genetics. Uncontrolled growth of cells. Not all tumors are cancerous Session8 Medical Genetics Cancer Genetics J avad Jamshidi F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s, N o v e m b e r 2 0 1 7 What is Cancer? Uncontrolled growth of cells Not all tumors

More information

What causes cancer? Physical factors (radiation, ionization) Chemical factors (carcinogens) Biological factors (virus, bacteria, parasite)

What causes cancer? Physical factors (radiation, ionization) Chemical factors (carcinogens) Biological factors (virus, bacteria, parasite) Oncogenes What causes cancer? Chemical factors (carcinogens) Physical factors (radiation, ionization) Biological factors (virus, bacteria, parasite) DNA Mutation or damage Oncogenes Tumor suppressor genes

More information

Revisiting post-translational regulation of cell cycle CDKs

Revisiting post-translational regulation of cell cycle CDKs Revisiting post-translational regulation of cell cycle CDKs Cyclin-CDK complexes during cell cycle Cyclin B-CDK1 G0 E2F prb Cyclin A-CDK1 G2 M Cyclin D-CDK4 CDK6 + prb Cyclin A-CDK2 S R G1 Cyclin E-CDK2

More information

THE HALLMARKS OF CANCER

THE HALLMARKS OF CANCER THE HALLMARKS OF CANCER ONCOGENES - Most of the oncogenes were first identified in retroviruses: EGFR (ErbB), Src, Ras, Myc, PI3K and others (slightly more than 30) - Mutated cellular genes incorporated

More information

Testicular stem cells

Testicular stem cells Testicular stem cells Dirk G. de Rooij Department of Endocrinology Faculty of Biology, Utrecht University 1. Knowledge on the development of the spermatogenic stem cell lineage 2. Principals of the nature

More information

Laboratory Considerations

Laboratory Considerations Laboratory Considerations In Support of HPV Vaccine Programs Elizabeth R. Unger PhD, MD Team Leader HPV Laboratory Centers for Disease Prevention and Control Towards Comprehensive Cervical Cancer Control:

More information

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy (Courtesy of Magda Stumpfova. Used with permission.) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. Navon, and A.L. Goldberg PNAS,

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

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

Review (V1) - The Hallmarks of Cancer

Review (V1) - The Hallmarks of Cancer Review (V1) - The Hallmarks of Cancer Robert A. Weinberg 1 Review (V1) - The Hallmarks of Cancer 2 Review (V1) - Number of somatic mutations in human cancers Top: children vs. adults Numbers in parentheses

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

Chapter 5 A Dose Dependent Screen for Modifiers of Kek5

Chapter 5 A Dose Dependent Screen for Modifiers of Kek5 Chapter 5 A Dose Dependent Screen for Modifiers of Kek5 "#$ ABSTRACT Modifier screens in Drosophila have proven to be a powerful tool for uncovering gene interaction and elucidating molecular pathways.

More information

Chem Lecture 2 Protein Structure

Chem Lecture 2 Protein Structure Chem 452 - Lecture 2 Protein Structure 110923 Proteins are the workhorses of a living cell and involve themselves in nearly all of the activities that take place in a cell. Their wide range of structures

More information

Gynecologic Malignancies. Kristen D Starbuck 4/20/18

Gynecologic Malignancies. Kristen D Starbuck 4/20/18 Gynecologic Malignancies Kristen D Starbuck 4/20/18 Outline Female Cancer Statistics Uterine Cancer Adnexal Cancer Cervical Cancer Vulvar Cancer Uterine Cancer Endometrial Cancer Uterine Sarcoma Endometrial

More information

REGULATORY MECHANISMS OF TRANSCRIPTION FACTOR FUNCTION

REGULATORY MECHANISMS OF TRANSCRIPTION FACTOR FUNCTION Transcription Regulation And Gene Expression in Eukaryotes Cycle G2 (lecture 13709) RG Clerc 04.04.2012 REGULATORY MECHANISMS OF TRANSCRIPTION FACTOR FUNCTION Protein synthesized Protein phosphorylated

More information