Bcl-2 inhibition of autophagy: a new route to cancer?
Bcl-2 was the first identified cellular protein that functions as an oncogene by blocking apoptotic cell death. Beclin 1, the first identified mammalian autophagy gene product, is a haploinsufficient tumor suppressor that was originally isolated as a Bcl-2-interacting protein. We recently showed that Bcl-2 negatively regulates Beclin 1-dependent autophagy and Beclin 1-dependent autophagic cell death. These findings raise the possibility that Bcl-2 family members may function as oncogenes not only by blocking apoptosis but also by blocking autophagy.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113, USA.
Sophie
S
Pattingre
Beth
B
Levine
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071186:Beclin-1; D019254:Genes, bcl-2 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009857:Oncogenes / Q000502:physiology; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2