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The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families.

The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, and Elongin C is a Skp1-like protein that binds to a BC-box motif that is present in both Elongin A and VHL and is distinct from the conserved F-box motif recognized by Skp1. In this report, we demonstrate that the Elongin BC complex also binds to a functional BC box present in the SOCS box, a sequence motif identified recently in the suppressor of cytokine signaling-1 (SOCS-1) protein, as well as in a collection of additional proteins belonging to the SOCS, ras, WD-40 repeat, SPRY domain, and ankyrin repeat families. In addition, we present evidence (1) that the Elongin BC complex is a component of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by binding to Jak2 and inhibiting Jak2 kinase, and (2) that by interacting with the SOCS box, the Elongin BC complex can increase expression of the SOCS-1 protein by inhibiting its degradation. These results suggest that Elongin BC is a multifunctional regulatory complex capable of controlling multiple pathways in the cell through interaction with a short degenerate sequence motif found in many different proteins.

Pubmed ID: 9869640


  • Kamura T
  • Sato S
  • Haque D
  • Liu L
  • Kaelin WG
  • Conaway RC
  • Conaway JW


Genes & development

Publication Data

December 15, 1998

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM41628

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Ankyrins
  • Binding Sites
  • Carrier Proteins
  • Cell Line
  • Consensus Sequence
  • Enzyme Stability
  • Gene Expression Regulation
  • Janus Kinase 2
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Rats
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Signal Transduction
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • ras Proteins