Apoptotic Pathways in Mammals Dr. Douglas R. Green

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Apoptotic Pathways in Mammals Dr. Douglas R. Green"

Transcription

1 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 at a predictable stage of development; It can be by apoptosis, but these terms are not synonymous 2 a b a Digits form during the development of the mammali an limb by programmed cell death; This cell death has the characteristics of apoptosis b From Choutan, M., et al., Current Biology 1999, 9: The screen versions of these slides have full details of copyright and acknowledgements 1

2 Blebbing Nuclear fragmentati on Chromatin condensati on Control Apoptosis 4 Joshua C. Goldstein and Douglas R. Green 5 Apoptosis Development Homeostasis Aging Loss of adhesion Oncogenesis (tumor suppressors) 6 The screen versions of these slides have full details of copyright and acknowledgements 2

3 Caspases (Cytokine processing) Inflammatory Inflammatory 7 Inactive executioner caspase Active caspase 8 Destroying the DNA Chromatin Activated executioner caspase icad-cad complex 9 The screen versions of these slides have full details of copyright and acknowledgements 3

4 Substrate cleavage Gelsolin M E KK- 1 P AK- 2 G el- DQ TD 352 G - solin Blebbing P A- EV D 212 G - K- 2 ICAD- L (- S) FAK F- VSW D 704 S - AK F- DQ TD 772 S- AK M E- DTV D 874 G - KK- 1 Loss of adhesion? D N A- P K I C- DE PD AD - L I C- DAV D AD - S DNA fragmentation PKC- δ PA RP D N A - D E V D N - P K P A - D E V D 213 G - RP Disable DNA repair? Ret inoblast oma PKC- DM Q D 330 N- δ Retino- DEAD 886 G - blastoma Disruption of cell cycle control? 10 Caspases Inflammatory Cleavage site 11 caspase activation Adapter caspase (activated) Cleavage and activation of executioner caspase caspase 12 The screen versions of these slides have full details of copyright and acknowledgements 4

5 Caspases Prodomains Death effector domain (DED) Caspase recruitment domain (CARD) Protease subunits Inflammatory Cleavage site 13 Death folds Death effector domain (DED) Caspase recruitment domain (CARD) Death domain (DD) Like-like interactions: DD-DD DED-DED CARD-CARD 14 Inhibitor of apoptosis proteins XIAP XIAP Caspase-3 Caspase-7 Caspase-9 Caspase-3 XIAP 15 Image from Reidl, et al., Cell Volume 104, Issue 5, 9 March 2001, Pages The screen versions of these slides have full details of copyright and acknowledgements 5

6 Apoptotic pathways in mammals Death receptor ( extrinsic ) pathway Death ligands Death receptors Mitochondrial ( intrinsic ) pathway Bcl-2 family Mitochondria Caspase 8 APAF-1 Caspase 9 16 Death receptors TNFR1 Fas Apo-1 CD95 Trail-R1 DR4 Apo-2 Trail-R2 DR5 Killer DR3 Apo-3 WSL TRAMP DR6 Subset of the TNFR family 17 Death receptors Death ligands DD DED DD FADD DED DED Death inducing signaling complex (DISC) Active caspase-8 procaspase-8 F AS T R AIL-receptors Cleavage and activation of executioner pro and apoptosis 18 The screen versions of these slides have full details of copyright and acknowledgements 6

7 TNF receptor TNF DD Other proteins TRAFs TRADD Complex I FADD Activation of NF-κB and antiapoptotic effects procaspase-8 Cleavage and activation of executioner pro and apoptosis Complex II Active caspase-8 19 Death receptor Death ligand DED DD FADD DED DED c-flip procaspase-8 blocked pro apoptosis 20 Apoptosisinducing signals Mitochondrial pathway of apoptosis Bcl-2 family proteins BH3-only protein Pro-apoptotic multidomain protein Anti-apoptotic Bcl-2 protein pro Cytochrome c Apoptosis protease activating factor (APAF-1) Procaspase-9 Active executioner Apoptosis Apoptosome 21 The screen versions of these slides have full details of copyright and acknowledgements 7

8 Green: cytochrome c Red (yellow): mitochondrial DY Blue: PS externalization Red: membrane integrity 22 Joshua C. Goldstein and Douglas R. Green Apoptosome Dome (caspase-9) Monomeric Apaf-1 WD WD cytochrome c Hub CARD Procaspase-9 23 Wild-type Knock-out APAF-1 Caspase-9 Cytochrome c K72A Kuida, et al., 1998 Cell 94, The screen versions of these slides have full details of copyright and acknowledgements 8

9 The Bcl-2 family proteins A n ti-apoptotic Bcl-2 homology (BH) domains P ro -apoptotic M ulti-domain B H 3-3 only 25 *adapted from Kuwana et al., 2003, drawn by J. Chipuk Bcl-2 family proteins with different functions have similar structures Anti-apoptotic (Bcl-xL) Pro-apoptotic multidomain (BAX) Pro-apoptotic BH3-only (BID) 26 The pro-apoptotic multidomain proteins Bax and Bak oligomerize upon activation and cause mitochondrial outer membrane permeabilization (MOMP) Ol igomerization Bax or Bak oligomers Bax oligomers M O M P and apoptosis Bax Monomeric Bax or Bak Bax alone +Buffer +Control protein +Active BID 27 The screen versions of these slides have full details of copyright and acknowledgements 9

10 Anti-apoptotic Bcl-2 proteins sequester direct activator BH3-only proteins Anti-apoptotic Bcl-2 proteins sequester direct activator BH3-only proteins B c l-xl l Liberated activator Activation and repression B ad Activation and de-repression De-repressor BH3-only protein Bim B c l-xl l B im Displace B ad B c l-xl l B im Other BH3-only proteins free them Activator BH3-only proteins trigger Bax and Bak to cause MOMP A ctivation Monomeric Bax or Bak Ol igomerization Bim A p optosis Bax or Bak oligomers 28 MOMP also promotes apoptosis inhibiting XIAP Smac OMI XIAP Caspase-3 Caspase-7 Caspase-9 29 The BH3-only protein BID bridges the death receptor and mitochondrial pathways 30 The screen versions of these slides have full details of copyright and acknowledgements 10

11 The mitochondrial pathway also leads to caspase-independent cell death Apoptosisinducing signals Anti-apoptotic Bcl-2 protein Bcl-2 Family Proteins BH3-only protein Pro-apoptotic multidomain protein Caspasedependent death pro Cas pase- independent deat h Los s of mitochondrial f unction APAF-1 Release of other t oxic molecules Procaspase-9 Apoptosome Apoptosis Active executioner 31 Cells die in the absence of caspase activation Control Apoptosis Caspases inhibited 32 Caspase independent cell death in the developing interdigital web Viable cell Apoptotic cell Dying cell in the web of an Apaf-1 -/- mouse 33 The screen versions of these slides have full details of copyright and acknowledgements 11

12 Apoptotic cells are eaten and removed from the system Phagocyte Don t eat me CD31 Find me Lysophosphatidylcholine Apoptotic cell Eat me (Externalization of phosphatidylserine, Other signals) 34 Phospholipids scramble in the plasma membrane during apoptosis Outer leaflet Phosphatidylserine Inner leaflet Lipid scrambling during apoptosis Annexin V binds phosphatidylserine MFG-8, Annexin I bind Dying cell recognized by phagocytes 35 Apoptotic pathways in mammals 36 The screen versions of these slides have full details of copyright and acknowledgements 12

13 37 The screen versions of these slides have full details of copyright and acknowledgements 13

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

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

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

Overview of cell death signaling pathways

Overview of cell death signaling pathways Cancer Biology & Therapy ISSN: 1538-4047 (Print) 1555-8576 (Online) Journal homepage: http://www.tandfonline.com/loi/kcbt20 Overview of cell death signaling pathways Zhaoyu Jin & Wafik S. El-Deiry To cite

More information

Types of cell death and apoptosis resistance mechanisms. Institut for Experimental Cancer Research

Types of cell death and apoptosis resistance mechanisms. Institut for Experimental Cancer Research Types of cell death and apoptosis resistance mechanisms Prof.Dr.rer. rer. nat.anna Trauzold Institut for Experimental Cancer Research Physiological cell death Embryogenesis Control of the tissue size Renewal

More information

Warner-Lambert/Parke-Davis Award Lecture

Warner-Lambert/Parke-Davis Award Lecture American Journal of Pathology, Vol. 157, No. 5, November 2000 Copyright American Society for Investigative Pathology Warner-Lambert/Parke-Davis Award Lecture Mechanisms of Apoptosis John C. Reed From The

More information

APPLICATION NOTE 1850 Millrace Drive, Suite 3A Eugene, Oregon

APPLICATION NOTE 1850 Millrace Drive, Suite 3A Eugene, Oregon APPLICATION NOTE 185 Millrace Drive, Suite 3A Eugene, Oregon 973 In-Cell ELISA (ICE) Assay Platform Monitoring apoptosis in cells: a high-throughput, quantitative cellbased assay. Rev. Introduction: Apoptosis:

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

2 The Extrinsic Pathway of Apoptosis

2 The Extrinsic Pathway of Apoptosis 2 The Extrinsic Pathway of Apoptosis M. Stacey Ricci, ScD, and Wafik S. El-Deiry, MD, PhD Summary Defects in the extrinsic pathway are linked to several disease states, including cancer. Pharmacologic

More information

Apoptosis and cancer. Cristina Muñoz Pinedo Bellvitge (IDIBELL)

Apoptosis and cancer. Cristina Muñoz Pinedo Bellvitge (IDIBELL) Apoptosis and cancer Cristina Muñoz Pinedo cmunoz@idibell.cat Institut d Investigació Biomèdica de Bellvitge (IDIBELL) Hanahan and Weinberg, Cell 2000 Apoptosis in cancer Tumors overexpress antiapoptotic

More information

Sensitization to death receptor stimuli and anchoragedependent cell death through induction of endoplasmic reticulum stress

Sensitization to death receptor stimuli and anchoragedependent cell death through induction of endoplasmic reticulum stress Sensitization to death receptor stimuli and anchoragedependent cell death through induction of endoplasmic reticulum stress by Kikanwa Brenda Lydia Hope Anyiwe A thesis submitted in conformity with the

More information

Cell cycle and apoptosis

Cell cycle and apoptosis Cell cycle and apoptosis Cell cycle Definition Stages and steps Cell cycle Interphase (G1/G0, S, and G2) Mitosis (prophase, metaphase, anaphase, telophase, karyokinesis, cytokinesis) Control checkpoints

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

THE EFFECT OF STEARIC ACID ON BREAST CANCER DEVELOPMENT AND PROGRESSION LYNDA MICHELE EVANS

THE EFFECT OF STEARIC ACID ON BREAST CANCER DEVELOPMENT AND PROGRESSION LYNDA MICHELE EVANS THE EFFECT OF STEARIC ACID ON BREAST CANCER DEVELOPMENT AND PROGRESSION by LYNDA MICHELE EVANS ROBERT W. HARDY, COMMITTEE CHAIR SUSAN L. BELLIS LISA M. SCHWIEBERT GENE P. SIEGAL DANNY R. WELCH ANNE WOODS

More information

The Annexin V Apoptosis Assay

The Annexin V Apoptosis Assay The Annexin V Apoptosis Assay Development of the Annexin V Apoptosis Assay: 1990 Andree at al. found that a protein, Vascular Anticoagulant α, bound to phospholipid bilayers in a calcium dependent manner.

More information

Apoptosis and Cell Death

Apoptosis and Cell Death 4 Apoptosis and Cell Death Pothana Saikumar and Manjeri A. Venkatachalam Introduction Cell death plays a central role in multicellular organisms during their early development in sculpting the body parts

More information

Epilepsy and apoptosis pathways

Epilepsy and apoptosis pathways Review Article David C Henshall 1 and Roger P Simon 2 & 2005 ISCBFM All rights reserved 0271-678X/05 $30.00 www.jcbfm.com 1 Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland,

More information

Tumor cells may respond to chemo- or radiotherapy by

Tumor cells may respond to chemo- or radiotherapy by PATHWAY OF THE MONTH Apoptotic Signaling Pathways in Lung Cancer Kristina Viktorsson, PhD* and Rolf Lewensohn, MD, PhD (J Thorac Oncol. 2007;2: 175 179) Tumor cells may respond to chemo- or radiotherapy

More information

INVESTIGATING APOPTOSIS PATHWAY IN CHRONIC LYMPHOCYTIC LEUKEMIA: STROMAL INFLUENCE AND THERAPEUTIC ACTIVATION

INVESTIGATING APOPTOSIS PATHWAY IN CHRONIC LYMPHOCYTIC LEUKEMIA: STROMAL INFLUENCE AND THERAPEUTIC ACTIVATION Texas Medical Center Library DigitalCommons@TMC UT GSBS Dissertations and Theses (Open Access) Graduate School of Biomedical Sciences 12-2013 INVESTIGATING APOPTOSIS PATHWAY IN CHRONIC LYMPHOCYTIC LEUKEMIA:

More information

Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives

Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives Chapter 5 Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: ovel Strategies and Futures Perspectives María A. García, Esther Carrasco, Alberto Ramírez, Gema Jiménez, Elena López-Ruiz,

More information

Role of Bcl-2 family proteins in apoptosis

Role of Bcl-2 family proteins in apoptosis Role of Bcl-2 family proteins in apoptosis The bcl-2 family proteins are involved in the response to apoptosis * pro-apoptotic: Bad, Bax or Bid cell death * anti-apoptotic: Bcl-2 and Bcl-XL cell survival

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

Molecular Mechanisms of Programmed Necrotic Death Initiated by Intrinsic Death Signals

Molecular Mechanisms of Programmed Necrotic Death Initiated by Intrinsic Death Signals Washington University in St. Louis Washington University Open Scholarship All Theses and Dissertations (ETDs) Spring 3-19-2014 Molecular Mechanisms of Programmed Necrotic Death Initiated by Intrinsic Death

More information

MEDIATION OF CHEMOTHERAPY-INDUCED APOPTOSIS BY THE LYSOSOMAL PROTEASE CATHEPSIN D. Lori Ann Emert-Sedlak. BS, Pennsylvania State University, 1999

MEDIATION OF CHEMOTHERAPY-INDUCED APOPTOSIS BY THE LYSOSOMAL PROTEASE CATHEPSIN D. Lori Ann Emert-Sedlak. BS, Pennsylvania State University, 1999 MEDIATION OF CHEMOTHERAPY-INDUCED APOPTOSIS BY THE LYSOSOMAL PROTEASE CATHEPSIN D by Lori Ann Emert-Sedlak BS, Pennsylvania State University, 1999 Submitted to the Graduate Faculty of The School of Medicine,

More information

DEATH AND ANTI-DEATH: TUMOUR RESISTANCE TO APOPTOSIS

DEATH AND ANTI-DEATH: TUMOUR RESISTANCE TO APOPTOSIS DEATH AND ANTI-DEATH: TUMOUR RESISTANCE TO APOPTOSIS Frederik H. Igney and Peter H. Krammer Every cell in a multicellular organism has the potential to die by apoptosis, but tumour cells often have faulty

More information

HDAC6 restricts acetylated survivin nuclear export By Matthew Thomas Riolo, B.S. Northeastern University, Boston MA, 2003

HDAC6 restricts acetylated survivin nuclear export By Matthew Thomas Riolo, B.S. Northeastern University, Boston MA, 2003 HDAC6 restricts acetylated survivin nuclear export By Matthew Thomas Riolo, B.S. Northeastern University, Boston MA, 2003 A Dissertation Submitted in Partial Fulfillment of the requirements for the Degree

More information

Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress

Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress Jean Y. J. WANG MINIREVIEW Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress Jean Y. J. WANG * Division of Biological Sciences and Moores Cancer Center, University

More information

APOPTOSIS IN CHRONIC LYMPHOCYTIC LEUKAEMIA

APOPTOSIS IN CHRONIC LYMPHOCYTIC LEUKAEMIA PhD Thesis APOPTOSIS IN CHRONIC LYMPHOCYTIC LEUKAEMIA Diane King BSc (Hons) Centre for Mechanisms of Human Toxicity and Department of Pathology University of Leicester UMI Number: U124012 All rights reserved

More information

NOVEMBER 27, 2009 VOLUME 284 NUMBER 48 JOURNAL OF BIOLOGICAL CHEMISTRY 33447

NOVEMBER 27, 2009 VOLUME 284 NUMBER 48 JOURNAL OF BIOLOGICAL CHEMISTRY 33447 THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 284, NO. 48, pp. 33447 33455, November 27, 2009 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. Caspase-9 Activation

More information

T cell maturation. T-cell Maturation. What allows T cell maturation?

T cell maturation. T-cell Maturation. What allows T cell maturation? T-cell Maturation What allows T cell maturation? Direct contact with thymic epithelial cells Influence of thymic hormones Growth factors (cytokines, CSF) T cell maturation T cell progenitor DN DP SP 2ry

More information

Cancer Translational Medicine

Cancer Translational Medicine CTM Review Cancer Translational Medicine Cancer Transl Med 2016;2(1):7 20 doi: 10.4103/2395-3977.177558 BCL2 Family, Mitochondrial Apoptosis, and Beyond Haiming Dai 1, X. Wei Meng 2, Scott H. Kaufmann

More information

Supplementary figure legends

Supplementary figure legends Supplementary figure legends Supplementary Figure 1. Exposure of CRT occurs independently from the apoptosisassociated loss of the mitochondrial membrane potential (MMP). (A) HeLa cells treated with MTX

More information

Cell Injury MECHANISMS OF CELL INJURY

Cell Injury MECHANISMS OF CELL INJURY Cell Injury MECHANISMS OF CELL INJURY The cellular response to injurious stimuli depends on the following factors: Type of injury, Its duration, and Its severity. Thus, low doses of toxins or a brief duration

More information

Basics of Radiation Biology

Basics of Radiation Biology Basics of Radiation Biology Sally A. Amundson Columbia University Center for Radiological Research http://www.cmcr.columbia.edu/ Overview Radiation damage to cells DNA Effects of radiation damage on cells

More information

Mitochondria - a target for anticancer therapy

Mitochondria - a target for anticancer therapy Institute of Environmental Medicine Division of Toxicology Karolinska Institutet, Stockholm, Sweden Mitochondria - a target for anticancer therapy Björn Kruspig Stockholm 2014 All previously published

More information

Chapter 2 TRAIL-R3/R4 and Inhibition of TRAIL Signalling in Cancer

Chapter 2 TRAIL-R3/R4 and Inhibition of TRAIL Signalling in Cancer Chapter 2 TRAIL-R3/R4 and Inhibition of TRAIL Signalling in Cancer Lubna Danish, Daniela Stöhr, Peter Scheurich, and Nadine Pollak Abstract The tumour necrosis factor (TNF) ligand family member TNF-related

More information

Viral Evasion Strategies

Viral Evasion Strategies Viral Evasion Strategies Lecture 15 Virology W3310/4310 Spring 2013 Don t look back, something might be gaining on you! -SATCHEL PAIGE Host vs. Virus What one does to the other? Evolution of strategies

More information

Therapeutic importance of apoptosis pathways in pancreatic cancer

Therapeutic importance of apoptosis pathways in pancreatic cancer FOLIA MEDICA CRACOVIENSIA Vol. LVI, 1, 2016: 61 70 PL ISSN 0015-5616 Therapeutic importance of apoptosis pathways in pancreatic cancer Aldona Olechowska-Jarząb 1, 2, Agata Ptak-Belowska 1, Tomasz Brzozowski

More information

Software development for the use of a mathematical prediction tool for chemotherapy responsiveness in a clinical and in a research environment

Software development for the use of a mathematical prediction tool for chemotherapy responsiveness in a clinical and in a research environment Royal College of Surgeons in Ireland e-publications@rcsi MSc by research theses Theses and Dissertations 1-1-2015 Software development for the use of a mathematical prediction tool for chemotherapy responsiveness

More information

Regulation of Mitochondria-dependent Apoptosis in Non-Small Cell Lung Cancer: Implications for Cancer Therapy. Agnieszka Chęcińska

Regulation of Mitochondria-dependent Apoptosis in Non-Small Cell Lung Cancer: Implications for Cancer Therapy. Agnieszka Chęcińska Regulation of Mitochondria-dependent Apoptosis in Non-Small Cell Lung Cancer: Implications for Cancer Therapy Agnieszka Chęcińska 1 The research described in this thesis was performed at the Department

More information

Development of a Human Lung Cancer Cytochrome C-GFP Reporter Cell Line to Study Anti-cancer Drug Responses in Apoptosis Pathways

Development of a Human Lung Cancer Cytochrome C-GFP Reporter Cell Line to Study Anti-cancer Drug Responses in Apoptosis Pathways City University of New York (CUNY) CUNY Academic Works Master's Theses City College of New York 2012 Development of a Human Lung Cancer Cytochrome C-GFP Reporter Cell Line to Study Anti-cancer Drug Responses

More information

Review article: APOPTOSIS: MOLECULAR MECHANISMS AND PATHOGENICITY

Review article: APOPTOSIS: MOLECULAR MECHANISMS AND PATHOGENICITY Review article: APPTSIS: MLECULAR MECHAISMS AD PATHGEICITY Rajesh P. Rastogi, Richa and Rajeshwar P. Sinha* Laboratory of Photobiology and Molecular Microbiology, Centre of Advanced Study in Botany, Banaras

More information

Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets

Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets Viruses2014, 6, 3181-3227; doi:10.3390/v6083181 Review OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets

More information

Memory and death in the immune system

Memory and death in the immune system Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Apoptosis Memory and death in the immune system Apoptosis refers to a

More information

ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY

ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY The recognition of specific antigen by naïve T cell induces its own activation and effector phases. T helper cells recognize peptide antigens through

More information

Review Article: THE POTENTIAL INTERVENTION ON APOPTOSIS AND CELL CYCLE ACTIVITY IN RHEUMATOID ARTHRITIS

Review Article: THE POTENTIAL INTERVENTION ON APOPTOSIS AND CELL CYCLE ACTIVITY IN RHEUMATOID ARTHRITIS The otential Intervention on Apoptosis and Cell Cycle Activity in Rheumatoid Arthritis (Joewono Soeroso) Review Article: THE OTENTIAL INTERVENTION ON AOTOSIS AND CELL CYCLE ACTIVITY IN RHEUMATOID ARTHRITIS

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

Bid induces cytochrome c-impermeable Bax channels in liposomes

Bid induces cytochrome c-impermeable Bax channels in liposomes Biochem. J. (2002) 363, 547 552 (Printed in Great Britain) 547 Bid induces cytochrome c-impermeable Bax channels in liposomes Xavier ROUOU*, Tatiana ROSTOVTSEVA, Sylvie MONTESSUIT*, Jean-laude MARTINOU*

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

NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2010 January 31.

NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2010 January 31. NIH Public Access Author Manuscript Published in final edited form as: Nature. 2009 April 30; 458(7242): 1127. doi:10.1038/nature07986. Cytoplasmic Functions of the Tumor Suppressor p53 Douglas R. Green

More information

Innate Immunity. Chapter 3. Connection Between Innate and Adaptive Immunity. Know Differences and Provide Examples. Antimicrobial peptide psoriasin

Innate Immunity. Chapter 3. Connection Between Innate and Adaptive Immunity. Know Differences and Provide Examples. Antimicrobial peptide psoriasin Chapter Know Differences and Provide Examples Innate Immunity kin and Epithelial Barriers Antimicrobial peptide psoriasin -Activity against Gram (-) E. coli Connection Between Innate and Adaptive Immunity

More information

Cell Signaling and Signal Transduction: Communication between Cells

Cell Signaling and Signal Transduction: Communication between Cells Cell Signaling and Signal Transduction: Communication between Cells - Cell signaling makes it possible for cells to respond in an appropriate manner to a specific environmental stimulus THE BASIC ELEMENTS

More information

Curriculum Vitae University of Maryland Baltimore; Baltimore, Maryland. Doctor of Philosophy, Molecular Medicine, May 2015

Curriculum Vitae University of Maryland Baltimore; Baltimore, Maryland. Doctor of Philosophy, Molecular Medicine, May 2015 Curriculum Vitae Name: Dominique R. Bollino Contact information: drbollino@gmail.com Degree and Date to be Conferred: Doctor of Philosophy, 2015 Collegiate Institutes Attended: 2009-2015 University of

More information

Cell Cell Communication

Cell Cell Communication IBS 8102 Cell, Molecular, and Developmental Biology Cell Cell Communication January 29, 2008 Communicate What? Why do cells communicate? To govern or modify each other for the benefit of the organism differentiate

More information

What determines the CD4:CD8 T cell ratio in the immune system?

What determines the CD4:CD8 T cell ratio in the immune system? What determines the CD4:CD8 T cell ratio in the immune system? Insights from genetic and mathematical modelling of thymocyte development Benedict Seddon 1 Cell of the immune system 2 Maintaining homeostasis

More information

Effector Mechanisms of Cell-Mediated Immunity

Effector Mechanisms of Cell-Mediated Immunity Effector Mechanisms of Cell-Mediated Immunity Dr. Julia Rempel Section of Hepatology 789-3825 jdrempel@cc.umanitoba.ca 804D JBRC Topics: I. Types of Cell-Mediated Immunity II. Migration of Effector T Lymphocytes

More information

Numbers in a Cell Population

Numbers in a Cell Population B. Control of Cell Number 1. Review of the mitotic cell cycle and cell death 2. Regulation of cell number and quality during mitosis 3. Regulation of cell type during mitosis Numbers in a Cell Population

More information

Beyond necroptosis: alternative pathways in necrotic cell death

Beyond necroptosis: alternative pathways in necrotic cell death Beyond necroptosis: alternative pathways in necrotic cell death PhD student: Andrea Tomasella Cellular Biology section Department of Medical and Biological Sciences University of Udine PhD course in Biomedical

More information

Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila

Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila Cellular Microbiology (27) 9(1), 246 264 doi:1.1111/j.1462-5822.26.785.x First published online 15 August 26 Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila Alaeddin Abu-Zant,

More information

Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells

Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells ORIGINAL ARTICLE Cell Research (2017) 27:764-783. www.nature.com/cr Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells Xinjian Liu 1, Fang Li 1, Qian Huang 2, Zhengxiang

More information

Experimental Dermatology, Department of Dermatology, TU Dresden, Dresden, Germany;

Experimental Dermatology, Department of Dermatology, TU Dresden, Dresden, Germany; Int. J. Mol. Sci. 2013, 14, 15260-15285; doi:10.3390/ijms140815260 Review OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms The Role of AKT/mTOR Pathway in

More information

Live or let die: posttranscriptional gene regulation in cell stress and cell death

Live or let die: posttranscriptional gene regulation in cell stress and cell death Marshall P. Thomas Judy Lieberman Live or let die: posttranscriptional gene regulation in cell stress and cell death Authors address Marshall P. Thomas 1, Judy Lieberman 1 1 Program in Cellular and Molecular

More information

Cell Death & Disease. Annika Hantusch 1,2,KushalK.Das 3, Ana J. García-Sáez 3, Thomas Brunner 1,2 and Markus Rehm 4,5,6,7

Cell Death & Disease. Annika Hantusch 1,2,KushalK.Das 3, Ana J. García-Sáez 3, Thomas Brunner 1,2 and Markus Rehm 4,5,6,7 Hantusch et al. Cell Death and Disease (2018) 9:430 DOI 10.1038/s41419-018-0464-6 Cell Death & Disease ARTICLE Bax retrotranslocation potentiates Bcl-x L s antiapoptotic activity and is essential for switch-like

More information

We are IntechOpen, the first native scientific publisher of Open Access books. International authors and editors. Our authors are among the TOP 1%

We are IntechOpen, the first native scientific publisher of Open Access books. International authors and editors. Our authors are among the TOP 1% We are IntechOpen, the first native scientific publisher of Open Access books 3,350 108,000 1.7 M Open access books available International authors and editors Downloads Our authors are among the 151 Countries

More information

Necroptosis in cardiac cells

Necroptosis in cardiac cells Necroptosis in cardiac cells Necroptosis; friend or foe during ischemia and reperfusion in cardiac cells by Christina Mathisen Heiestad Thesis for the Master`s degree (MSc) in Molecular Biosciences (60

More information

Mechanisms and clinical implications of hepatocyte lipoapoptosis

Mechanisms and clinical implications of hepatocyte lipoapoptosis Clinical Lipidology ISSN: 1758-4299 (Print) 1758-4302 (Online) Journal homepage: http://www.tandfonline.com/loi/tlip20 Mechanisms and clinical implications of hepatocyte lipoapoptosis Sophie C Cazanave

More information

The past decade has experienced

The past decade has experienced Elucidating the Fundamental Mechanisms of Cell Death Triggered by Photothermal Therapy Jilian R. Melamed, Rachel S. Edelstein, and Emily S. Day* Biomedical Engineering, University of Delaware, Newark,

More information

Supplementary Figure 1

Supplementary Figure 1 Supplementary Figure 1 Expression of apoptosis-related genes in tumor T reg cells. (a) Identification of FOXP3 T reg cells by FACS. CD45 + cells were gated as enriched lymphoid cell populations with low-granularity.

More information

PUMA, A CRITICAL MEDIATOR OF CELL DEATH ONE DECADE ON FROM ITS DISCOVERY. University of Łódź, ul. Pomorska 141/143, Łódź, Poland

PUMA, A CRITICAL MEDIATOR OF CELL DEATH ONE DECADE ON FROM ITS DISCOVERY. University of Łódź, ul. Pomorska 141/143, Łódź, Poland CELLULAR & MOLECULAR BIOLOGY LETTERS http://www.cmbl.org.pl Received: 19 March 2012 Volume 17 (2012) pp 646-669 Final form accepted: 07 September 2012 DOI: 10.2478/s11658-012-0032-5 Published online: 20

More information

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway Sebastián Zamorano 1,2, Diego Rojas-Rivera 1,2, Fernanda Lisbona 1,2, Valentina Parra 2,3, Felipe A. Court 4, Rosario Villegas 4, Emily

More information

Lipotoxic Lethal and Sublethal Stress Signaling in Hepatocytes: Relevance to NASH Pathogenesis

Lipotoxic Lethal and Sublethal Stress Signaling in Hepatocytes: Relevance to NASH Pathogenesis Lipotoxic Lethal and Sublethal Stress Signaling in Hepatocytes: Relevance to NASH Pathogenesis Petra Hirsova 1, Samar H. Ibrabim 2, Gregory J. Gores 1, Harmeet Malhi 1 1 Division of Gastroenterology and

More information

Sildenafil and celecoxib interact to kill breast cancer cells

Sildenafil and celecoxib interact to kill breast cancer cells Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2014 Sildenafil and celecoxib interact to kill breast cancer cells Brittany Binion Virginia Commonwealth University,

More information

2005 NSIS Graduate Student Prize Winning Paper CLEAR AS MUD: THE TYPE I/TYPE II MODEL FOR DEATH RECEPTOR-INDUCED APOPTOSIS

2005 NSIS Graduate Student Prize Winning Paper CLEAR AS MUD: THE TYPE I/TYPE II MODEL FOR DEATH RECEPTOR-INDUCED APOPTOSIS PROC. N.S. INST. SCI. (2006) Volume 43, Part 2, pp. 201-209 2005 NSIS Graduate Student Prize Winning Paper CLEAR AS MUD: THE TYPE I/TYPE II MODEL FOR DEATH RECEPTOR-INDUCED APOPTOSIS DAVID MICHAEL CONRAD

More information

BH3-Only Protein BIM Mediates Heat Shock-Induced Apoptosis

BH3-Only Protein BIM Mediates Heat Shock-Induced Apoptosis BH3-Only Protein BIM Mediates Heat Shock-Induced Apoptosis Indra M. Mahajan 1,2, Miao-Der Chen 1,2, Israel Muro 2, John D. Robertson 3, Casey W. Wright 2, Shawn B. Bratton 1 * 1 The University of Texas

More information

In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-X L and Mcl-1 but in the absence of active BH3-only proteins

In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-X L and Mcl-1 but in the absence of active BH3-only proteins OPEN Citation: (2015) 6, e1996; doi:10.1038/cddis.2015.341 & 2015 Macmillan Publishers Limited All rights reserved 2041-4889/15 www.nature.com/cddis In non-transformed cells Bak activates upon loss of

More information

CARCINOGENESIS: THE MOLECULAR BASIS OF CANCER

CARCINOGENESIS: THE MOLECULAR BASIS OF CANCER CARCINOGENESIS: THE MOLECULAR BASIS OF CANCER Nonlethal genetic damage lies at the heart of carcinogenesis. Mutation may be acquired by the action of environmental agents, such as chemicals, radiation,

More information

Apoptosis. Sebas&ano Ba+aglia, PhD. Dept. Pharmacology and Therapeu&cs Roswell Park Cancer Ins&tute

Apoptosis. Sebas&ano Ba+aglia, PhD. Dept. Pharmacology and Therapeu&cs Roswell Park Cancer Ins&tute Apoptosis Sebas&ano Ba+aglia, PhD Dept. Pharmacology and Therapeu&cs Roswell Park Cancer Ins&tute Reference books The Biology of Cancer (Robert Weinberg) + other online references What is Apoptosis Role

More information

Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function

Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function Casey W. Wright 1 and Colin S. Duckett 1,2 1 Department of Pathology, and 2 Department of Internal Medicine,

More information

The Hallmarks of Cancer

The Hallmarks of Cancer The Hallmarks of Cancer Theresa L. Hodin, Ph.D. Clinical Research Services Theresa.Hodin@RoswellPark.org Hippocrates Cancer surgery, circa 1689 Cancer Surgery Today 1971: Nixon declares War on Cancer

More information

Anti-Apoptotic Effects of Cellular Therapy

Anti-Apoptotic Effects of Cellular Therapy Anti-Apoptotic Effects of Cellular Therapy Jason Lapetoda 1, Lee K Landeen, PhD 1, George K Michalopoulos, MD 2, Patricia W Bedard, PhD 1 1 Vital Therapies, Inc., San Diego, CA, USA 2 University of Pittsburgh

More information

Bioactivity Assays: Putting the Puzzle Together

Bioactivity Assays: Putting the Puzzle Together Bioactivity Assays: Putting the Puzzle Together Dr. Ulrike Herbrand Department for Biosafety & Bioassay Services Charles River Biologics Testing Solutions Outline General Remarks MoA reflecting bioassays

More information

Plasma membrane changes during programmed cell deaths

Plasma membrane changes during programmed cell deaths REVIEW Cell Research (2018) 28:9-21. www.nature.com/cr Plasma membrane changes during programmed cell deaths Yingying Zhang 1, Xin Chen 1, Cyril Gueydan 2, Jiahuai Han 1 1 State Key Laboratory of Cellular

More information

Bcl-2 family members regulate the sensitivity to 2-deoxy-D-glucose in lymphomas

Bcl-2 family members regulate the sensitivity to 2-deoxy-D-glucose in lymphomas University of Iowa Iowa Research Online Theses and Dissertations Fall 2011 Bcl-2 family members regulate the sensitivity to 2-deoxy-D-glucose in lymphomas Oksana Zagorodna University of Iowa Copyright

More information

JBC Papers in Press. Published on February 1, 2017 as Manuscript M

JBC Papers in Press. Published on February 1, 2017 as Manuscript M JBC Papers in Press. Published on February 1, 2017 as Manuscript M116.754184 The latest version is at http://www.jbc.org/cgi/doi/10.1074/jbc.m116.754184 ROS induced by sorafenib overcomes TRAIL resistance

More information

Neutrophils in the Pathogenesis of Sepsis

Neutrophils in the Pathogenesis of Sepsis Neutrophils in the Pathogenesis of Sepsis John C. Marshall, MD FRCSC St. Michael s Hospital Critical Care Canada Forum 2012 Toronto, Canada October 29, 2012 University of Toronto Thanks to Songhui Jia

More information

Functional Role of Glycogen synthase Kinase-3 on Glucocorticoid-mediated signaling

Functional Role of Glycogen synthase Kinase-3 on Glucocorticoid-mediated signaling Functional Role of Glycogen synthase Kinase-3 on Glucocorticoid-mediated signaling Camila Rubio Patiño ADVERTIMENT. La consulta d aquesta tesi queda condicionada a l acceptació de les següents condicions

More information

Apoptosis, autophagy, necroptosis, and cancer metastasis

Apoptosis, autophagy, necroptosis, and cancer metastasis Su et al. Molecular Cancer (2015) 14:48 DOI 10.1186/s12943-015-0321-5 REVIEW Open Access Apoptosis, autophagy, necroptosis, and cancer metastasis Zhenyi Su 1,2, Zuozhang Yang 3,4*, Yongqing Xu 4, Yongbin

More information

Silencing of Pokemon Enhances Caspase-Dependent Apoptosis via Fas- and Mitochondria-Mediated Pathways in Hepatocellular Carcinoma Cells

Silencing of Pokemon Enhances Caspase-Dependent Apoptosis via Fas- and Mitochondria-Mediated Pathways in Hepatocellular Carcinoma Cells Silencing of Pokemon Enhances Caspase-Dependent Apoptosis via Fas- and Mitochondria-Mediated Pathways in Hepatocellular Carcinoma Cells Yu-Qin Zhang 1., Chuan-Xing Xiao 1., Bi-Yun Lin 1, Ying Shi 1, Yun-Peng

More information

Apoptosis of human umbilical vein endothelial cells (HUVEC) induced by IgA1 isolated from Henoch- Schonlein purpura children

Apoptosis of human umbilical vein endothelial cells (HUVEC) induced by IgA1 isolated from Henoch- Schonlein purpura children Original article Apoptosis of human umbilical vein endothelial cells (HUVEC) induced by IgA1 isolated from Henoch- Schonlein purpura children Ping Yuan, 1 Yan Bo, 2 Gui Ming, 1 Fei Wen-Jun, 1 Zhang Qin

More information

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis Mireille Laforge 1., Laure Campillo-Gimenez 1., Valérie Monceaux 2, Marie-Christine Cumont 2, Bruno Hurtrel 2, Jacques Corbeil 3, John

More information

Innate immunity. Abul K. Abbas University of California San Francisco. FOCiS

Innate immunity. Abul K. Abbas University of California San Francisco. FOCiS 1 Innate immunity Abul K. Abbas University of California San Francisco FOCiS 2 Lecture outline Components of innate immunity Recognition of microbes and dead cells Toll Like Receptors NOD Like Receptors/Inflammasome

More information

Chapter 9 Signal Transduction and Cell Growth

Chapter 9 Signal Transduction and Cell Growth Part II Principles of Individual Cell Function Chapter 9 One characteristic of organisms is that they exhibit various behaviors in response to changes in their environment (i.e., the outside world). Cells

More information

NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update

NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update NNZ-2566 in Rett Syndrome and Autism Spectrum Disorders Role and Update 1 Overview The natural growth factor IGF-1 is broken down in the body to IGF-1[1-3] NNZ-2566 is an analogue of IGF-1[1-3] developed

More information

Clinical Trial News on the Treatment of Waldenstrom s Macroglobulinemia

Clinical Trial News on the Treatment of Waldenstrom s Macroglobulinemia Clinical Trial News on the Treatment of Waldenstrom s Macroglobulinemia Edward Libby M.D. Associate Professor, University of Washington Department of Medicine, Division of Medical Oncology Fred Hutchinson

More information

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment DOI:http://dx.doi.org/10.7314/APJCP.2015.16.6.2129 Molecular Mechanisms of Apoptosis and its Role in Cancer Development and Treatment REVIEW Molecular Mechanisms of Apoptosis and Roles in Cancer Development

More information

Xiangning Zhang, M.B., Med. Lic.

Xiangning Zhang, M.B., Med. Lic. Immunogenicity of and apoptosis modulation by Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1): implications for nasopharyngeal carcinoma Xiangning Zhang, M.B., Med. Lic. Stockholm 2005

More information