FLASH Coordinates NF-κB Activity via TRAF2

Yun Hee Choi, Ki Bae Kim, Hyun Hee Kim, Gil Sun Hong, Yun Kyung Kwon, Chul Woong Chung, Yang Mi Park, Zhong Jian Shen, Byung Ju Kim, Soo Young Lee, Yong Keun Jung

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38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)25073-25077
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number27
DOIs
StatePublished - Jul 6 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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. (2001). FLASH Coordinates NF-κB Activity via TRAF2. Journal of Biological Chemistry, 276(27), 25073-25077. https://doi.org/10.1074/jbc.M102941200