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

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.

Pubmed ID: 17053147


  • Dorrello NV
  • Peschiaroli A
  • Guardavaccaro D
  • Colburn NH
  • Sherman NE
  • Pagano M


Science (New York, N.Y.)

Publication Data

October 20, 2006

Associated Grants

  • Agency: NCI NIH HHS, Id: R01-CA76584
  • Agency: NIGMS NIH HHS, Id: R01-GM57587

Mesh Terms

  • 5' Untranslated Regions
  • Amino Acid Motifs
  • Apoptosis Regulatory Proteins
  • Binding Sites
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Size
  • Eukaryotic Initiation Factor-4A
  • Eukaryotic Initiation Factor-4F
  • Eukaryotic Initiation Factor-4G
  • Eukaryotic Initiation Factors
  • Humans
  • Mitogens
  • Phosphorylation
  • Protein Biosynthesis
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Ribosomal Protein S6 Kinases
  • SKP Cullin F-Box Protein Ligases
  • Serine
  • Serum
  • Signal Transduction
  • beta-Transducin Repeat-Containing Proteins