The BioGRID | PUBLICATION VIEW

	J. Biol. Chem. Jul (2001); 276(27):25073-7
FLASH coordinates NF-kappa B activity via TRAF2.
Choi YH, Kim KB, Kim HH, Hong GS, Kwon YK, Chung CW, Park YM, Shen ZJ, Kim BJ, Lee SY, Jung YK
Department of Life Science, Kwangju Institute of Science and Technology, Puk-gu, Kwangju 500-712, Korea.
Abstract: 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.
[PUBMED: 11340079]