The Elongin BC complex interacts with the conserved SOCS-box motif presentin 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 co mplex, in which it participates in both tumor suppression and negative regu lation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, a nd Elongin C is a Skp1-like protein that binds to a BC-box motif that is pr esent in both Elongin A and VHL and is distinct from the conserved F-box mo tif 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 sequen ce motif identified recently in the suppressor of cytokine signaling-1 (SOC S-1) protein, as well as in a collection of additional proteins belonging t o 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 compone nt of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by b inding 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 m otif found in many different proteins.