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Fas-associated Factor-1 Inhibits Nuclear Factor-κB (NF-κB) Activity by Interfering with Nuclear Translocation of the RelA (p65) Subunit of NF-κB

Title
Fas-associated Factor-1 Inhibits Nuclear Factor-κB (NF-κB) Activity by Interfering with Nuclear Translocation of the RelA (p65) Subunit of NF-κB
Authors
Park M.-Y.Jang H.D.Lee S.Y.Lee K.-J.Kim E.
Ewha Authors
이공주이수영
SCOPUS Author ID
이공주scopus; 이수영scopus
Issue Date
2004
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 279, no. 4, pp. 2544 - 2549
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Fas-associated factor-1 (FAF1) is a Fas-binding proapoptotic protein that is a component of the death-inducing signaling complex in Fas-mediated apoptosis. Here, we show that FAF1 is involved in negative regulation of NF-κB activation. Overexpression of FAF1 decreased the basal level of NF-κB activity in 293 cells. NF-κB activation induced by tumor necrosis factor (TNF)-α, interleukin-1β, and lipopolysaccharide was also inhibited by FAF1 overexpression. Moreover, FAF1 suppressed NF-κB activation induced by transducers of diverse NF-κB-activating signals such as TNF receptor-associated factor-2 and -6, MEKK1, and IκB kinase-β as well as NF-κB p65, one of the end point molecules in the NF-κB activation pathway, suggesting that NF-κB p65 might be a target molecule upon which FAF1 acts. Subsequent study disclosed that FAF1 physically interacts with NF-κB p65 and that the binding domain of FAF1 is the death effector domain (DED)-interacting domain (amino acids 181-381), where DEDs of the Fas-associated death domain protein and caspase-8 interact. The NF-κB activity-modulating potential of FAF1 was also mapped to the DED-interacting domain. Finally, overexpression of FAF1 prevented translocation of NF-κB p65 into the nucleus and decreased its DNA-binding activity upon TNFα treatment. This study presents a novel function of FAF1, in addition to the previously known function as a component of the Fas death-inducing signaling complex, i.e. NF-κB activity suppressor by cytoplasmic retention of NF-κB p65 via physical interaction.
DOI
10.1074/jbc.M304565200
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약학대학 > 약학과 > Journal papers
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