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

Research output: Contribution to journalArticle

37 Citations (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.

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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TNF Receptor-Associated Factor 2
HEK293 Cells
TNF Receptor-Associated Factor 5
Death Domain Receptor Signaling Adaptor Proteins
TNF Receptor-Associated Factor 6
Effector Caspases
Caspase 8
Antisense Oligonucleotides
Cell Extracts
Luciferases
Reporter Genes
HeLa Cells
Gene expression
Chemical activation
Apoptosis
Gene Expression
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Choi, Y. H., Kim, K. B., Kim, H. H., Hong, G. S., Kwon, Y. K., Chung, C. W., ... 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

FLASH Coordinates NF-κB Activity via TRAF2. / Choi, Yun Hee; Kim, Ki Bae; Kim, Hyun Hee; Hong, Gil Sun; Kwon, Yun Kyung; Chung, Chul Woong; Park, Yang Mi; Shen, Zhong Jian; Kim, Byung Ju; Lee, Soo Young; Jung, Yong Keun.

In: Journal of Biological Chemistry, Vol. 276, No. 27, 06.07.2001, p. 25073-25077.

Research output: Contribution to journalArticle

Choi, YH, Kim, KB, Kim, HH, Hong, GS, Kwon, YK, Chung, CW, Park, YM, Shen, ZJ, Kim, BJ, Lee, SY & Jung, YK 2001, 'FLASH Coordinates NF-κB Activity via TRAF2', Journal of Biological Chemistry, vol. 276, no. 27, pp. 25073-25077. https://doi.org/10.1074/jbc.M102941200
Choi YH, Kim KB, Kim HH, Hong GS, Kwon YK, Chung CW et al. FLASH Coordinates NF-κB Activity via TRAF2. Journal of Biological Chemistry. 2001 Jul 6;276(27):25073-25077. https://doi.org/10.1074/jbc.M102941200
Choi, Yun Hee ; Kim, Ki Bae ; Kim, Hyun Hee ; Hong, Gil Sun ; Kwon, Yun Kyung ; Chung, Chul Woong ; Park, Yang Mi ; Shen, Zhong Jian ; Kim, Byung Ju ; Lee, Soo Young ; Jung, Yong Keun. / FLASH Coordinates NF-κB Activity via TRAF2. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 27. pp. 25073-25077.
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