2004
DOI: 10.1074/jbc.m403286200
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Regulation of the NF-κB-inducing Kinase by Tumor Necrosis Factor Receptor-associated Factor 3-induced Degradation

Abstract: The NF-B family of transcription factors plays a pivotal role in regulation of diverse biological processes, including immune responses, cell growth, and apoptosis. Activation of NF-B is mediated by both canonical and noncanonical signaling pathways. Although the canonical pathway has been extensively studied, the mechanism mediating the noncanonical pathway is still poorly understood. Recent studies have identified the NF-B-inducing kinase (NIK) as a key component of the noncanonical pathway of NF-B activatio… Show more

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Cited by 427 publications
(496 citation statements)
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“…This function is mediated by TRAF3, which interacts with these receptors. TRAF3 negatively regulates NIK, and undergoes signal-dependent degradation resulting in the activation of the non-canonical pathway (Liao et al, 2004).…”
Section: Tnf-r Superfamily Signalingmentioning
confidence: 99%
“…This function is mediated by TRAF3, which interacts with these receptors. TRAF3 negatively regulates NIK, and undergoes signal-dependent degradation resulting in the activation of the non-canonical pathway (Liao et al, 2004).…”
Section: Tnf-r Superfamily Signalingmentioning
confidence: 99%
“…TRAF3 serves as an adaptor molecule that allows for the assembly of a complex involving NIK, TRAF2 and activated cIAPs, which causes TRAF3 itself to be modified by K48-linked ubiquitination by cIAPs [60,61]. As NIK protein expression is regulated by TRAF3, signal-induced proteosomal degradation of TRAF3 leads to accumulation of NIK protein and activation of the downstream pathway [62,63]. Increase in NIK protein results in phosphorylation of p100 at Ser866 and Ser870, and activation of IKK1 [64,65].…”
Section: The Non-canonical Pathwaymentioning
confidence: 99%
“…293, ts20 and MEF cells were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and 2 mM l-glutamine. Ramos RG69 and M12.4.1 cells were cultured in RPMI supplemented with 10% fetal bovine serum, 2 mM l-glutamine and 10 mM 2-mercaptoethanol [11,12]. ts20 cells were usually maintained at 35 °C instead of 37 °C.…”
Section: Cell Culture and Transfectionmentioning
confidence: 99%
“…Induction of this process strictly depends on NF-κB-inducing kinase (NIK) and its downstream kinase IKKα (α subunit of IκB kinase, also named IKK1) [5,6], and is mediated only by a limited number of stimuli, such as lymphotoxin beta (LTb), B-cell activating factor (BAFF) and CD40 ligand (CD40L) [2,[6][7][8][9][10]. One important function of these stimuli is to prevent basally translated NIK protein from undergoing degradation mediated by the tumor necrosis factor receptor-associated factor 3 (TRAF3) [11][12][13]. Stabilized NIK in turn specifically activates and recruits IKKα into the p100 complex via serines 866 and 870 of p100 [14].…”
Section: Introductionmentioning
confidence: 99%