Article

S6K1- and beta TRCP-mediated degradation of PDCD4 promotes protein translation and cell growth

University of Virginia, Charlottesville, Virginia, United States
Science (Impact Factor: 31.48). 11/2006; 314(5798):467-71. DOI: 10.1126/science.1130276
Source: PubMed

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 Ser67 by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF(betaTRCP). Expression in cultured cells of a stable PDCD4 mutant that is unable to bind betaTRCP 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.

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