Gene interactions and pathways from curated databases and text-mining
Science 2006, PMID: 17053147

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

Dorrello, N Valerio; Peschiaroli, Angelo; Guardavaccaro, Daniele; Colburn, Nancy H; Sherman, Nicholas E; Pagano, Michele

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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Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: UBC — PDCD4 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: BTRC — PDCD4 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4A1 — EIF4G1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF3B — EIF4A1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CTNNB1 — BTRC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4A1 — PDCD4 (physical association, affinity chromatography technology)
  • IRef Innatedb Interaction: BTRC — CTNNB1 (unknown, -)
  • NCI Pathway Database mTOR signaling pathway: PDCD4 (PDCD4) → beta TrCP1-2 (FBXW11/BTRC) (proteasomal ubiquitin-dependent protein catabolic process, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: PDCD4 (PDCD4) → eIF4A (EIF4A1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: PDCD4 (PDCD4) → PDCD4/eIF4A complex (PDCD4-EIF4A1) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: p70S6K (RPS6KB1) → eIF4A (EIF4A1) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: p70S6K (RPS6KB1) → PDCD4/eIF4A complex (PDCD4-EIF4A1) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database mTOR signaling pathway: eIF4A (EIF4A1) → PDCD4/eIF4A complex (PDCD4-EIF4A1) (modification, collaborate)
    Evidence: mutant phenotype, assay
In total, 11 gene pairs are associated to this article in curated databases