Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retinoblastoma tumor suppressor (pRb) is thought to orchestrate terminal differentiation by inhibiting cell proliferation and apoptosis and stimulating lineage-specific transcription factors. In this study, we show that in the absence of pRb, differentiating primary myoblasts fuse to form short myotubes that never twitch and degenerate via a nonapoptotic mechanism. The shortened myotubes exhibit an impaired mitochondrial network, mitochondrial perinuclear aggregation, autophagic degradation, and reduced adenosine triphosphate production. Bcl-2 and autophagy inhibitors restore mitochondrial function and rescue muscle degeneration, leading to formation of long, twitching myotubes that express normal levels of muscle-specific proteins and stably exit the cell cycle. A hypoxia-induced glycolytic switch also rescues the myogenic defect after either chronic or acute inactivation of Rb in a hypoxia-inducible factor-1 (HIF-1)-dependent manner. These results demonstrate that pRb is required to inhibit apoptosis in myoblasts and autophagy in myotubes but not to activate the differentiation program, and they also reveal a novel link between pRb and cell metabolism.
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PMID:Rescue of myogenic defects in Rb-deficient cells by inhibition of autophagy or by hypoxia-induced glycolytic shift. 2093 98