Human ubiquitin specific protease 31 is a deubiquitinating enzyme implicated in activation of nuclear factor-κB

TRAF2 mediates activation of the transcription factors NF-kappa B and AP1 by TNF. A yeast two-hybrid screen of a human cDNA library identified a ubiquitin specific protease homologue (USP31) as a TRAF2-interacting protein. Two cDNAs encoding for USP31 were identified. One cDNA encodes a 1035-amino acid long isoform of USP31 (USP31, long isoform) and the other a 485-amino acid long isoform of USP31 (USP31S1, short isoform). USP31 and USP31 SI share a common amino terminal region with homology to the catalytic region of known deubiquitinating enzymes. Enzymatic assays demonstrated that USP31 but not USP31 SI possess deubiquitinating activity. Furthermore, it was shown that USP3 I has a higher activity towards lysine-63-linked as compared to lysine-48-linked polyubiquitin chains. Overexpression of USP31 in HEK 293Tcells inhibited TNF alpha, CD40, LMP1, TRAF2, TRAF6 and IKK beta-mediated NF-kappa B activation, but did not inhibit Smad-mediated transcription activation. In addition, both USP31 isoforms interact with p65/RelA. Our data support a role for USP31 in the regulation of NF-kappa B activation by members of the TNF receptor superfamily. (c) 2005 Elsevier Inc. All rights reserved.