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FLASH Coordinates NF-κB Activity via TRAF2

Title
FLASH Coordinates NF-κB Activity via TRAF2
Authors
Choi Y.-H.Kim K.-B.Kim H.-H.Hong G.-S.Kwon Y.-K.Chung C.-W.Park Y.-M.Shen Z.-J.Kim B.J.Lee S.-Y.Jung Y.-K.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2001
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 276, no. 27, pp. 25073 - 25077
Indexed
SCI; SCIE; SCOPUS WOS scopus
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 anti-sense oligonucleotide-induced inhibition of FLASH expression abolished TNF-α-induced activation of NF-κB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-κB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-κB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKα, 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-κB 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-κB activity via a TRAF2-dependent pathway in the TNF-α signaling.
DOI
10.1074/jbc.M102941200
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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