The Bcl-2 (Bcl is B-cell lymphocytic-leukaemia proto-oncogene) family comprises two groups of proteins with distinct functional biology in cell-fate signalling. Bcl-2 protein was the first member to be discovered and associated with drug resistance in human lymphomas. Since then a host of other proteins such as Bcl-xL, Bcl-2A1 and Mcl-1 with similar anti-apoptotic functions have been identified. In contrast, the pro-apoptotic Bcl-2 proteins contain prototypic effector proteins such as Bax and Bak, and the BH3 (Bcl-2 homology)-only proteins comprising Bak, Bid, Bim, Puma and Noxa. A complex interplay between the association of pro-apoptotic and anti-apoptotic proteins with each other determines the sensitivity of cancer cells to drug-induced apoptosis. The canonical functional of Bcl-2 in terms of apoptosis inhibition is its ability to prevent mitochondrial permeabilization via inhibiting the translocation and oligomerization of pro-apoptotic proteins such as Bax; however, more recent evidence points to a novel mechanism of the anti-apoptotic activity of Bcl-2. Overexpression of Bcl-2 increases mitochondrial oxygen consumption and in doing so generates a slight pro-oxidant intracellular milieu, which promotes genomic instability and blocks death signalling. However, in the wake of overt oxidative stress, Bcl-2 regulates cellular redox status thereby preventing excessive build-up of ROS (reactive oxygen species), which is detrimental to cells and tissues. Taken together, the canonical and non-canonical activities of Bcl-2 imply a critical involvement of this protein in the processes of tumour initiation and progression. In the present paper we review these functionally distinct outcomes of Bcl-2 expression with implications for the chemotherapeutic management of cancers.
Skip Nav Destination
Article navigation
May 2011
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Review Article|
April 13 2011
Regulation of mitochondrial metabolism: yet another facet in the biology of the oncoprotein Bcl-2
Shefali Krishna;
Shefali Krishna
*Apoptosis, ROS and Cancer Biology Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Search for other works by this author on:
Ivan Cherh Chiet Low;
Ivan Cherh Chiet Low
*Apoptosis, ROS and Cancer Biology Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
†NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117597, Singapore
Search for other works by this author on:
Shazib Pervaiz
Shazib Pervaiz
1
*Apoptosis, ROS and Cancer Biology Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
†NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117597, Singapore
‡Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore 117597, Singapore
§Singapore–MIT Alliance, Singapore
1To whom correspondence should be addressed (email phssp@nus.edu.sg).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 29 2010
Revision Received:
February 10 2011
Accepted:
February 11 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 435 (3): 545–551.
Article history
Received:
November 29 2010
Revision Received:
February 10 2011
Accepted:
February 11 2011
Citation
Shefali Krishna, Ivan Cherh Chiet Low, Shazib Pervaiz; Regulation of mitochondrial metabolism: yet another facet in the biology of the oncoprotein Bcl-2. Biochem J 1 May 2011; 435 (3): 545–551. doi: https://doi.org/10.1042/BJ20101996
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.