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

Takumi Kamura, Shigeo Sato, Dewan Haque, Li Liu, William G. Kaelin, Ronald C. Conaway, Joan Weliky Conaway

Research output: Contribution to journalArticlepeer-review

493 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3872-3881
Number of pages10
JournalGenes and Development
Volume12
Issue number24
DOIs
StatePublished - Dec 15 1998
Externally publishedYes

Keywords

  • Elongin BC complex
  • Jak/STAT signaling
  • Protein degradation
  • SOCS box
  • SOCS-1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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