Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes.
Incubation of hepatocytes under hypoxia increases binding of translation initiation factor eIF-4E to its inhibitory regulator 4E-BP1, and this correlates with dephosphorylation of 4E-BP1. Rapamycin induced the same effect in aerobic cells but no additive effect was observed when hypoxic cells were treated with rapamycin. This enhanced association of 4E-BP1 with eIF-4E might be mediated by mTOR. Nevertheless, only hypoxia produces a rapid inhibition of protein synthesis. Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia.
Tinton
S A
SA
Unité de Biochimie Toxicologique et Cancérologique, Université Catholique de Louvain, Brussels, Belgium.
Buc-Calderon
P M
PM
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002352:Carrier Proteins; D015687:Cell Hypoxia; D002478:Cells, Cultured; D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology
D000935:Antifungal Agents; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D020123:Sirolimus