Molecular and Cellular Biochemistry

, Volume 351, Issue 1–2, pp 41–58 | Cite as

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

Article

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.

Keywords

Apoptosis Bcl-2 BH-3 only proteins Caspases Mitochondrial proteins Programmed cell death 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Mohammad Shamsul Ola
    • 1
  • Mohd. Nawaz
    • 1
  • Haseeb Ahsan
    • 2
  1. 1.Department of OphthalmologyCollege of Medicine, King Saud UniversityRiyadhKSA
  2. 2.Department of Biochemistry, Faculty of DentistryJamia Millia Islamia (A Central University)New DelhiIndia

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