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FEBS Lett. 1999 Mar 5;446(1):55-9.

Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytes.

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Unité de Biochimie Toxicologique et Cancérologique, Université Catholique de Louvain, Brussels, Belgium.


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.

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