Identification of a cell protein (FIP-3) as a modulator of NF-κB activity and as a target of an adenovirus inhibitor of tumor necrosis factor α-induced apoptosis

Li, Yongan; Kang, Jian; Friedman, Joshua M.; Tarassishin, Leonid; Ye, Jianjiang; Kovalenko, Andrew; Wallach, David; Horwitz, Marshall S.

doi:10.1073/pnas.96.3.1042

Cited by 165 publications

(150 citation statements)

References 50 publications

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“…These results provide a genetic proof for the importance of IKK in NF-kB activation and suggest that the C-terminal region of IKKg is necessary for recruitment of upstream activators (presumably IKK-kinases or IKK-Ks). In addition, overexpression of IKKg can inhibit IKK activation due to titration of limiting IKK activators that remain to be identi®ed (Li et al, 1999b).…”

Section: Ikb Kinase and Its Regulationmentioning

confidence: 99%

How NF-κB is activated: the role of the IκB kinase (IKK) complex

1999

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Rel/NF-kB transcription factors are primarily regulated by association with inhibitor IkB proteins. Thus, in most cells NF-kB exists in the cytoplasm in an inactive complex bound to IkB. Most agents that activate NF-kB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IkB. The key regulatory step in this pathway involves activation of a high molecular weight IkB kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKKa and IKKb subunits. This review describes the identi®cation of proteins in the IKK complex, and the regulation and physiological functions of IKK.

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Section: Ikb Kinase and Its Regulationmentioning

confidence: 99%

How NF-κB is activated: the role of the IκB kinase (IKK) complex

1999

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“…IKKs are part of a large 900-kDa kinase complex that also includes the regulatory subunit NEMO (NF-B essential modulator), also known as IKK␥ or FIP3 (30)(31)(32). The essential role of NEMO͞IKK␥ in activating the NF-B pathway is based, in part, on the inability of NEMO-deficient cell lines to respond to NF-B activating signals, including lipopolysaccharide, IL-1, and Tax (31,33).…”

mentioning

confidence: 99%

CIKS, a connection to IκB kinase and stress-activated protein kinase

Leonardi

Chariot

Claudio

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

149

155

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“…The IKK complex is composed of IKK␣ and IKK␤ kinases bound to a scaffolding protein, IKK␥ (10)(11)(12)(13). Gene knockouts (KOs) indicate that IKK␤ and IKK␥ are core components for almost all nuclear translocation of RelA DNA-binding complexes, whereas IKK␣ is not essential (11,14,15).…”

mentioning

confidence: 99%

Epstein–Barr virus latent membrane protein 1 activation of NF-κB through IRAK1 and TRAF6

Luftig

Prinarakis

Yasui

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

123

153

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Epstein–Barr virus latent membrane protein 1 (LMP1) activation of NF-κB is critical for Epstein–Barr virus-infected B lymphocyte survival. LMP1 activates the IκB kinase complex and NF-κB through two cytoplasmic signaling domains that engage tumor necrosis factor receptor-associated factor (TRAF)1/2/3/5 or TRADD and RIP. We now use cells lacking expression of TRAF2, TRAF5, TRAF6, IKKα, IKKβ, IKKγ, TAB2, IL-1 receptor-associated kinase (IRAK)1, or IRAK4 to assess their roles in LMP1-mediated NF-κB activation. LMP1-induced RelA nuclear translocation was similar in IKKα knockout (KO) and WT murine embryo fibroblasts (MEFs) but substantially deficient in IKKβ KO MEFs. NF-κB-dependent promoter responses were also substantially deficient in IKKβ KO MEFs but were hyperactive in IKKα KO MEFs. More surprisingly, NF-κB responses were near normal in TRAF2 and TRAF5 double-KO MEFs, IKKγ KO MEFs, TAB2 KO MEFs, and IRAK4 KO MEFs but were highly deficient in TRAF6 KO MEFs and IRAK1 KO HEK293 cells. Consistent with the importance of TRAF6, LMP1-induced NF-κB activation in HEK293 cells was inhibited by expression of dominant-negative TAB2 and Ubc13 alleles. These data extend a role for IKKα in IKKβ regulation, identify an unusual IKKβ-dependent and IKKγ-independent NF-κB activation, and indicate that IRAK1 and TRAF6 are essential for LMP1-induced NF-κB activation.

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Identification of a cell protein (FIP-3) as a modulator of NF-κB activity and as a target of an adenovirus inhibitor of tumor necrosis factor α-induced apoptosis

Cited by 165 publications

References 50 publications

How NF-κB is activated: the role of the IκB kinase (IKK) complex

How NF-κB is activated: the role of the IκB kinase (IKK) complex

CIKS, a connection to IκB kinase and stress-activated protein kinase

Epstein–Barr virus latent membrane protein 1 activation of NF-κB through IRAK1 and TRAF6

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