Lontar KomputerPub Date : 2001-07-06Epub Date: 2001-05-04DOI: 10.1074/jbc.M102941200
Y H Choi, K B Kim, H H Kim, G S Hong, Y K Kwon, C W Chung, Y M Park, Z J Shen, B J Kim, S Y Lee, Y K Jung
{"title":"FLASH coordinates NF-kappa B activity via TRAF2.","authors":"Y H Choi, K B Kim, H H Kim, G S Hong, Y K Kwon, C W Chung, Y M Park, Z J Shen, B J Kim, S Y Lee, Y K Jung","doi":"10.1074/jbc.M102941200","DOIUrl":"10.1074/jbc.M102941200","url":null,"abstract":"<p><p>FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.</p>","PeriodicalId":31196,"journal":{"name":"Lontar Komputer","volume":"7 1","pages":"25073-7"},"PeriodicalIF":0.0,"publicationDate":"2001-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1074/jbc.M102941200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90887381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}