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Role of Bcl-2 family proteins and caspases in the regulation of apoptosis

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Abstract

Apoptosis, or programmed cell death, plays a pivotal role in the elimination of unwanted, damaged, or infected cells in multicellular organisms and also in diverse biological processes, including development, cell differentiation, and proliferation. Apoptosis is a highly regulated form of cell death, and dysregulation of apoptosis results in pathological conditions including cancer, autoimmune and neurodegenerative diseases. The Bcl-2 family proteins are key regulators of apoptosis, which include both anti- and pro-apoptotic proteins, and a slight change in the dynamic balance of these proteins may result either in inhibition or promotion of cell death. Execution of apoptosis by various stimuli is initiated by activating either intrinsic or extrinsic pathways which lead to a series of downstream cascade of events, releasing of various apoptotic mediators from mitochondria and activation of caspases, important for the cell fate. In view of recent research advances about underlying mechanism of apoptosis, this review highlights the basics concept of apoptosis and its regulation by Bcl-2 family of protein. Furthermore, this review discusses the interplay of various apoptotic mediators and caspases to decide the fate of the cell. We expect that this review will add to the pool of basic information necessary to understand the mechanism of apoptosis which may implicate in designing better strategy to develop biomedical therapy to control apoptosis.

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Abbreviations

PCD:

Programmed cell death

Bcl-2:

B cell lymphoma-2 protein

Bax:

Bcl-2 associated X protein

Bid:

Bcl-2 interacting domain death agonist

Bad:

Bcl-2 antagonist of cell death

Bcl-xl:

Bcl-extra long

Bim:

Bcl-2 interacting mediator of cell death

Bik:

Bcl-2 interacting killer

Bmf:

Bcl-2 modifying factor

Boo:

Bcl-2 homolog of ovary

Bcl-xs:

Bcl-extra short

Bak:

Bcl-2 antagonistic killer

Bok:

Bcl-2 related ovarian killer

Apaf-1:

Apoptosis protease-activating factor-1

Diablo:

Direct IAP binding Protein with low pI

FADD:

Fas-associated death domain protein

TNF-R:

Tumor necrosis factor receptor

Fas-L:

Fas ligand

HtrA:

High-temperature requirement

IAP:

Inhibitor of apoptosis protein

IMM:

Inner mitochondrial membrane

Omi/HtrA2:

Mammalian serine protease

SMAC:

Second mitochondrial activator of caspase

TNF-α:

Tumor Necrosis Factor alpha

TRADD:

TNF-receptor-1 associated death domain protein

VDAC:

Voltage-dependent anion channel

Cyt c:

Cytochrome c

PIDDosome:

p53-Inducible death domain containing protein complex

DISC:

Death-inducing signaling complex

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Acknowledgments

MSO and MN thank Medical Research Chair in Ophthalmology funded by Dr. Nasser Al-Rasheed, College of Medicine, Kind Saud University for support. HA would like to thank Dr. Nihal Ahmad, School of Medicine and Public Health, University of Wiscosnsin, Madison for a cancer cell biology research fellowship. The authors would also like to thank Ms. Crisalis Longanilla-Bautista and Mr. Miaraj Siddiquei in helping with figures and proof reading.

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Correspondence to Haseeb Ahsan.

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Ola, M.S., Nawaz, M. & Ahsan, H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351, 41–58 (2011). https://doi.org/10.1007/s11010-010-0709-x

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  • DOI: https://doi.org/10.1007/s11010-010-0709-x

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