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

  1. Takumi Kamura1,2,
  2. Shigeo Sato2,
  3. Dewan Haque1,2,
  4. Li Liu2,
  5. William G. Kaelin, Jr.3,4,
  6. Ronald C. Conaway2, and
  7. Joan Weliky Conaway1,2,5,6
  1. 1Howard Hughes Medical Institute (HHMI) and 2Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104 USA; 3Howard Hughes Medical Institute and Dana-Farber Cancer Institute, Boston, Massachusetts 02115 USA; 4Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115 USA; 5Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190 USA

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.

Keywords

Footnotes

  • 6 Corresponding author.

  • E-MAIL conawayj{at}omrf.ouhsc.edu; FAX (405) 271-1580.

    • Received August 17, 1998.
    • Accepted November 6, 1998.
| Table of Contents

Life Science Alliance