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Archives of Toxicology

, Volume 89, Issue 3, pp 289–317 | Cite as

The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update

  • Waseem Ahmad Siddiqui
  • Amjid Ahad
  • Haseeb AhsanEmail author
Review Article

Abstract

Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.

Keywords

Bcl-2 Apoptosis BH3 Mitochondria Cancer Neurodegenerative disorders Extrinsic pathway 

Abbreviations

TNF-α

Tumor necrosis factor alpha

TNFR1

Tumor necrosis factor receptor 1

FasL

Fatty acid synthetase ligand, Fas ligand

FasR

Fatty acid synthetase receptor, Fas receptor

Apo3L

Apo3 ligand

DR3

Death receptor 3

TRAIL

TNF-related apoptosis-inducing ligand

DR4

Death receptor 4

DR5

Death receptor 5

FADD

Fas-associated death domain

TRADD

TNF receptor-associated death domain

RIP

Receptor-interacting protein

DED

Death effector domain

Caspase

Cysteinyl aspartic acid protease

FLICE

FADD-like ICE

c-FLIP

FLICE-inhibitory protein

Smac/DIABLO

Second mitochondrial activator of caspases/direct IAP-binding protein with low PI

IAP

Inhibitor of apoptosis proteins

Apaf-1

Apoptotic protease-activating factor

AIF

Apoptosis-inducing factor

CAD

Caspase-activated DNase

Bcl-2

B cell lymphoma protein 2

Bcl-x

Bcl-2-like 1

Bcl-XL

Bcl-2-related protein long form of Bcl-x

Bcl-XS

Bcl-2-related protein short isoform

Bcl-w

Bcl-2-like 2 protein

BAG

Bcl-2-associated athanogene

Bcl-10

B cell lymphoma protein 10

Bax

Bcl-2-associated X protein

Bak

Bcl-2 antagonist killer 1

Bid

BH3-interacting domain

Bad

Bcl-2 antagonist of cell death Bcl-2-binding protein

Bim

Bcl-2-interacting protein

Bik

Bcl-2-interacting killer

Blk

Bik-like killer protein

Puma

Bcl-2-binding component 3

Noxa

Phorbol-12-myristate-13-acetate-induced protein 1

14-3-3

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein

Aven

Cell death regulator Aven none

Myc

Oncogene myc

PARP

Poly(ADP-ribose) polymerase ADP ribosyltransferase

NuMA

Nuclear mitotic apparatus protein

CAD

Caspase-activated DNase

ICAD

Inhibitor of CAD

Notes

Acknowledgments

This review article is dedicated to Dr. Nihal Ahmad and Dr. Hasan Mukhtar, Professors at the School of Medicine and Public Health, University of Wisconsin, Madison (USA). The authors sincerely appreciate the valuable and encouraging comments of the editor(s) and reviewer(s).

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Waseem Ahmad Siddiqui
    • 1
  • Amjid Ahad
    • 1
  • Haseeb Ahsan
    • 2
    Email author
  1. 1.Department of Biochemistry, Faculty of ScienceJamia Hamdard (Hamdard University)New DelhiIndia
  2. 2.Department of Biochemistry, Faculty of DentistryJamia Millia IslamiaNew DelhiIndia

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