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.
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
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
Genes Dev.
Date: Dec. 15, 1998
PubMed ID: 9869640
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