Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment

Cristina Correia, Sun Hee Lee, X. Wei Meng, Nicole D. Vincelette, Katherine L.B. Knorr, Husheng Ding, Grzegorz S. Nowakowski, Haiming Dai, Scott H. Kaufmann

Research output: Contribution to journalReview articlepeer-review

96 Scopus citations

Abstract

Bcl-2, the founding member of a family of apoptotic regulators, was initially identified as the protein product of a gene that is translocated and overexpressed in greater than 85% of follicular lymphomas (FLs). Thirty years later we now understand that anti-apoptotic Bcl-2 family members modulate the intrinsic apoptotic pathway by binding and neutralizing the mitochondrial permeabilizers Bax and Bak as well as a variety of pro-apoptotic proteins, including the cellular stress sensors Bim, Bid, Puma, Bad, Bmf and Noxa. Despite extensive investigation of all of these proteins, important questions remain. For example, how Bax and Bak breach the outer mitochondrial membrane remains poorly understood. Likewise, how the functions of anti-apoptotic Bcl-2 family members such as eponymous Bcl-2 are affected by phosphorylation or cancer-associated mutations has been incompletely defined. Finally, whether Bcl-2 family members can be successfully targeted for therapeutic advantage is only now being investigated in the clinic. Here we review recent advances in understanding Bcl-2 family biology and biochemistry that begin to address these questions.

Original languageEnglish (US)
Pages (from-to)1658-1671
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • Activation-induced cytidine deaminase
  • Apoptosis
  • BH3 mimetic
  • Follicular lymphoma
  • Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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