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Am J Cancer Res. 2012;2(2):214-21. Epub 2012 Feb 15.

Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch.

Author information

1
University of Kansas, Department of Molecular Biosciences Lawrence, Kansas, USA. rtmarquez@ku.edu; xul@ku.edu

Abstract

Cancer cells have developed novel mechanisms for evading chemotherapy-induced apoptosis and autophagy-associated cell death pathways. Upon the discovery that chemotherapeutics could target these cell death pathways in a manner that was not mutually exclusive, new discoveries about the interrelationship between these two pathways are emerging. Key proteins originally thought to be "autophagy-related proteins" are now found to be involved in either inducing or inhibiting apoptosis. Similarly, apoptosis inhibiting proteins can also block autophagy-associated cell death. One example is the complex formed by the autophagy protein, Beclin 1, and anti-apoptotic protein Bcl-2, which leads to inhibition of autophagy-associated cell death. Researchers have been investigating additional mechanisms that form/disrupt this complex in order to better design chemotherapeutics. This review will highlight the role Bcl-2 and Beclin 1 play in cancer development and drug resistance, as well as the role the Bcl-2:Beclin 1 complex in the switch between autophagy and apoptosis.

KEYWORDS:

Apoptosis; BH3 mimetics; Bcl-2; Beclin 1; Gossypol; autophagy

PMID:
22485198
PMCID:
PMC3304572

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