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

ArticleinScience 314(5798):467-71 · November 2006with35 Reads
Impact Factor: 33.61 · 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 SCFβTRCP. 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.