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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kamura T,Sato S,Haque D,Liu L,Kaelin WG Jr,Conaway RC,Conaway JWdoi
10.1101/gad.12.24.3872subject
Has Abstractpub_date
1998-12-15 00:00:00pages
3872-81issue
24eissn
0890-9369issn
1549-5477journal_volume
12pub_type
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doi:10.1101/gad.5.11.2000
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pub_type: 杂志文章
doi:10.1101/gad.13.7.798
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pub_type: 杂志文章
doi:10.1101/gad.10.17.2158
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