Abstract

The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5′ untranslated region (5′UTR) of messenger RNAs (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser 67 by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF βTRCP . Expression in cultured cells of a stable PDCD4 mutant that is unable to bind βTRCP inhibited translation of an mRNA with a structured 5′UTR, resulted in smaller cell size, and slowed down cell cycle progression. We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth.

Keywords

RNA Helicase ACell biologyUbiquitin ligaseUntranslated regionMessenger RNAeIF4AProtein biosynthesisTranslation (biology)BiologyFive prime untranslated regionCell cycleCell growthRNAMolecular biologyP70-S6 Kinase 1ChemistryCellUbiquitinBiochemistrySignal transductionHelicaseGenePI3K/AKT/mTOR pathway

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Year
2006
Type
article
Volume
314
Issue
5798
Pages
467-471
Citations
697
Access
Closed

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N. Valerio Dorrello, Angelo Peschiaroli, Daniele Guardavaccaro et al. (2006). S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth. Science , 314 (5798) , 467-471. https://doi.org/10.1126/science.1130276

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DOI
10.1126/science.1130276