Many players in BCL-2 family affairs

Trends Biochem Sci. 2014 Mar;39(3):101-11. doi: 10.1016/j.tibs.2013.12.006. Epub 2014 Feb 3.

Abstract

During apoptotic cell death, cellular stress signals converge at the mitochondria to induce mitochondrial outer-membrane permeabilization (MOMP) through B cell lymphoma-2 (BCL-2) family proteins and their effectors. BCL-2 proteins function through protein-protein interactions, the mechanisms and structural aspects of which are only now being uncovered. Recently, the elucidation of the dynamic features underlying their function has highlighted their structural plasticity and the consequent complex thermodynamic landscape governing their protein-protein interactions. These studies show that canonical interactions involve a conserved, hydrophobic groove, whereas non-canonical interactions function allosterically outside the groove. We review the latest structural advances in understanding the interactions and functions of mammalian BCL-2 family members, and discuss new opportunities to modulate these proteins in health and disease.

Keywords: B cell lymphoma-2 (BCL-2) family proteins; mitochondrial apoptosis; mitochondrial outer-membrane permeabilization (MOMP).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Humans
  • Mitochondrial Membranes / metabolism*
  • Permeability
  • Proto-Oncogene Proteins c-bcl-2* / chemistry
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2