title: TRAF-interacting protein (TRIP) is a RING-dependent ubiquitin ligase.
abstract: TRAF-interacting protein (TRIP) was initially identified as a TRAF1- and TRAF2-binding partner that inhibited NF-kappaB activation without a known mechanism. Inspection of the TRIP sequence revealed an N-terminal RING domain, which is found in many E3 ubiquitin (Ub) ligases. We show that TRIP is a RING-dependent Ub ligase that undergoes auto-ubiquitination and requires an intact RING domain. Both TRIP and its RING mutant interact with TRAF1, 2, 3, 5, and 6, but failed to interact with CYLD and NIK. Stable expression of TRIP or a RING mutant did not affect IKK activation induced by TNF or IL-1 and had no affect on TNF-induced apoptosis. Similarly, RANKL-induced signaling and osteoclastogenesis were not affected by TRIP or its RING mutant. Interestingly, TRIP expression was down regulated during the late stages of osteoclastogenesis. Taken together, our results demonstrate that TRIP is a novel RING-dependent Ub ligase and a binding partner for TRAFs.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Box 143, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Besse
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Campos
authors.forename: William K
authors.initials: WK
authors.lastname: Webster
authors.forename: Bryant G
authors.initials: BG
authors.lastname: Darnay
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D000074749:Deubiquitinating Enzyme CYLD; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000074749:Deubiquitinating Enzyme CYLD; D051550:I-kappa B Kinase; D007375:Interleukin-1; D017346:Protein Serine-Threonine Kinases; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D000097782:NF-kappaB-Inducing Kinase; C409984:CYLD protein, human