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


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.


Bcl-2 Apoptosis BH3 Mitochondria Cancer Neurodegenerative disorders Extrinsic pathway 



Tumor necrosis factor alpha


Tumor necrosis factor receptor 1


Fatty acid synthetase ligand, Fas ligand


Fatty acid synthetase receptor, Fas receptor


Apo3 ligand


Death receptor 3


TNF-related apoptosis-inducing ligand


Death receptor 4


Death receptor 5


Fas-associated death domain


TNF receptor-associated death domain


Receptor-interacting protein


Death effector domain


Cysteinyl aspartic acid protease




FLICE-inhibitory protein


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


Inhibitor of apoptosis proteins


Apoptotic protease-activating factor


Apoptosis-inducing factor


Caspase-activated DNase


B cell lymphoma protein 2


Bcl-2-like 1


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


Bcl-2-related protein short isoform


Bcl-2-like 2 protein


Bcl-2-associated athanogene


B cell lymphoma protein 10


Bcl-2-associated X protein


Bcl-2 antagonist killer 1


BH3-interacting domain


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


Bcl-2-interacting protein


Bcl-2-interacting killer


Bik-like killer protein


Bcl-2-binding component 3


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


Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein


Cell death regulator Aven none


Oncogene myc


Poly(ADP-ribose) polymerase ADP ribosyltransferase


Nuclear mitotic apparatus protein


Caspase-activated DNase


Inhibitor of CAD



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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