S6K1- and ßTRCP-Mediated Degradation of PDCD4 Promotes Protein Translation and Cell Growth

• DOI: 10.1126/science.1130276
• Publication Date: 2006-10-19T20:53:14Z
• Authors: N. Valerio Dorrello; Angelo Peschiaroli; Daniele Guardavac...; Nancy H. Colburn; Nicholas E. Sherman; Michele Pagano
• Keywords: RNA Helicase A; eIF4A

The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes unwinding of secondary structure at 5' untranslated region (5'UTR) messenger RNAs (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser67 by kinase S6K1 and subsequently degraded via ubiquitin ligase SCF(betaTRCP). Expression in cultured cells a stable mutant is unable bind betaTRCP inhibited mRNA with structured 5'UTR, resulted smaller size, slowed down cycle progression. We propose regulated degradation mitogens allows efficient synthesis consequently growth.