ライフサイエンスコーパス: NIK

1 NIK activation triggers the noncanonical NF-kappaB trans

2 NIK and its upstream BAFF receptor regulate B-cell expre

3 NIK cleavage requires the concerted actions of both fusi

4 NIK depletion also resulted in reduced expression of gen

5 NIK expression is negatively regulated by the full-lengt

6 NIK interacts with the second baculovirus IAP repeat (BI

7 NIK is activated by a broad spectrum of stimuli.

8 NIK is brought into close proximity to the c-IAPs throug

9 NIK is often highly expressed in tumor cells, including

10 NIK is the first kinase shown to phosphorylate and incre

11 NIK levels are elevated in pancreatic islets isolated fr

12 NIK mediated the TNF-alpha activation of inhibitory kapp

13 NIK promotes mitochondrial fission, velocity, and direct

14 NIK transgenic Tregs competed poorly with WT Tregs in vi

15 NIK-activated noncanonical NF-kappaB signaling induces p

16 NIK-dependent NF-kappaB activation downstream of several

17 NIK-depleted melanoma cells exhibited downregulation of

18 NIK/IKK-alpha axis regulated the activation of both NF-k

19 Our findings identify a NIK-SIX signalling axis that fine-tunes inflammatory gen

20 expression of chemokine-encoding genes in a NIK-dependent manner.

21 ssociated factor 3 (Traf3) as formation of a NIK-Traf3-Traf2 complex targets NIK for degradation.

22 Lastly, we have used a NIK inhibitor that reduced HL but not other B-cell lymph

23 in contrast to cytokine-mediated activation, NIK stabilization by MACs did not involve cIAP2 or TRAF3

24 canonical NF-kappaB by forming a novel Akt(+)NIK(+) signalosome on Rab5(+) endosomes.

25 pendent not only on TRAF1 induction but also NIK stabilization by forming TRAF1.NIK complex.

26 Although NIK has been extensively studied for its function in the

27 Although NIK was not necessary for antigen receptor signaling, it

28 kout mice, we here demonstrate that although NIK is dispensable for thymocyte development, it has a c

29 beta caused a rapid activation of MEKK-1 and NIK.

30 ear p50 occurred in IKKbeta-, IKKgamma-, and NIK-defective MEFs, indicating that this induction is no

31 of TRAF3 ablated binding of both LTbetaR and NIK suggesting a common recognition site.

32 ponents, including NFkappaB2/p100, RelB, and NIK, accompanied by processing of NFkappaB2/p100 into p5

33 urther examine the interactions of TRAF1 and NIK with NF-kappaB2/p100 processing, we mathematically m

34 ze MAC, triggering both endosomal-associated NIK-dependent NLRP3 inflammasome assembly and IL-1 synth

35 demonstrating that RP3 disrupts normal basal NIK regulation.

36 Because NIK-deficient mice lack secondary lymphoid organs, we ge

37 We established a strong link between NIK(+) ECs, (pre)FDCs, and the presence of TLSs, indicat

38 We studied the relation between NIK(+) ECs, (pre)FDCs, and ILC3s with respect to TLSs in

39 TRAF2 inhibited cIAP interaction and blocked NIK degradation.

40 NLRP12 interacted with both NIK and TRAF3, and Nlrp12(-/-) cells have constitutively

41 reactivated in differentiated macrophages by NIK-mediated suppression of the ubiquitin proteasome pat

42 loop of IKKalpha, which is phosphorylated by NIK, did not develop inflammatory disease.

43 ighly expressed by adrenal chromaffin cells, NIK-related kinase, a gene on the X-chromosome, results

44 In cells, NIK kinase activity was necessary for increased Arp2 pho

45 The T cell-conditional NIK knockout mice were also defective in generation of i

46 Using T cell-conditional NIK knockout mice, we here demonstrate that although NIK

47 Our conditional NIK-knockout mice may be broadly useful for assessing th

48 Under normal conditions, NIK is targeted for continuous degradation by a tumor ne

49 tory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammato

50 We found that constitutive NIK expression decreased expression of numerous Treg sig

51 We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ a

52 Here, we show that constitutive NIK expression that is restricted to Tregs via a Cre-ind

53 Cytoplasmic NIK expression as well as NF-kappaB2/ Bcl3 detection was

54 Cytosolic NIK, stabilized by LIGHT (lymphotoxin-like inducible pro

55 The resulting deregulated NIK activity is associated with constitutive noncanonica

56 the ligated LTbetaR competitively displaced NIK from TRAF3.

57 irpin RNA techniques were used to knock-down NIK, the resultant NIK-depleted melanoma cell lines exhi

58 rp12(-/-) cells have constitutively elevated NIK, p100 processing to p52 and reduced TRAF3.

59 llelic mutation in the MAP3K14 gene encoding NIK (NF-kappaB-inducing kinase).

60 Systemic deletion of Map3k14, encoding NIK, resulted in reduced glucagon responses and hepatic

61 ab5+MAC+NIK+ endosomes followed by endosomal NIK-dependent inflammasome assembly.

62 Together, these findings establish NIK as a cell-intrinsic mediator of T cell functions in

63 Excessive NIK activity is implicated in various disorders, such as

64 on of ex-Foxp3(+) T cells in mice expressing NIK constitutively in Tregs, and these former Tregs prod

65 ated gene 1 (NDRG1) in MCPyV gene-expressing NIKs and hTERT-MCPyV gene-expressing human keratinocytes

66 Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to

67 y ECs in vivo and was similarly required for NIK stabilization and EC activation.

68 ha/beta) and NF-kappaB, are not required for NIK to regulate cell invasion, Drp1 mitochondrial locali

69 cs, we demonstrate that Drp1 is required for NIK-dependent, cytokine-induced invasion.

70 dentified a T cell-intrinsic requirement for NIK in graft-versus-host disease (GVHD), wherein NIK-def

71 demonstrate a cell-intrinsic requirement for NIK in the generation and/or maintenance of memory T cel

72 uminate a critical T cell-intrinsic role for NIK during immune responses and suggest that its tight r

73 r data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-o

74 Our data suggest a crucial role for NIK in mediating the generation of effector T cells and

75 Consistent with a role for NIK in regulating mitochondrial dynamics, we demonstrate

76 serum IgA, which is indicative of roles for NIK in additional pathways beyond BAFF signaling.

77 cimens revealed strong positive staining for NIK.

78 lymphocytic form of HES, CD4(+) T cells from NIK-deficient mice express increased levels of Th2-assoc

79 bone marrow chimeras using bone marrow from NIK knockout (KO) and wild-type (WT) donor mice and infe

80 placement of NIK and TRAF degradation halted NIK turnover, and promoted its association with IKKalpha

81 Hepatic NIK was abnormally activated in mice with dietary or gen

82 the hepatocyte NIK-liver immune cell axis promotes liver inflammation,

83 In primary mouse hepatocytes, NIK overexpression stimulated, independently of cell inj

84 olated mouse livers and primary hepatocytes, NIK also promoted glucagon action and glucose production

85 ments, relatively fewer activated (CD44(hi)) NIK KO T cells were present, but within the CD44(hi) pop

86 e first crystal structure of truncated human NIK in complex with adenosine 5'-O-(thiotriphosphate) at

87 We identify NIK as a critical negative regulator of beta cell functi

88 argets (e.g. Lcn2 and A20), as well as IKK1, NIK, and RelB, but no changes in markers of inflammation

89 halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression

90 n obscured by other developmental defects in NIK-deficient mice.

91 wed a statistically significant elevation in NIK expression when compared with benign nevi (n=30).

92 , however, demonstrated that inflammation in NIK-deficient mice depended on radiation-resistant tissu

93 nase (NIK) and did not activate NF-kappaB in NIK-deficient MEFs.

94 nstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity.

95 ceptor-associated factor 3, which results in NIK kinase accumulation, IkappaBalpha phosphorylation, a

96 g hematopoietic stem cell transplantation in NIK deficiency.

97 These upregulated NMD targets included NIK mRNA, which encodes a potent activator of NF-kappaB.

98 hibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene

99 noncanonical NF-kappaB signaling, including NIK, and immunohistochemical analysis revealed that NIK

100 alpha and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of th

101 establish a new paradigm for IKK-independent NIK signaling and significantly expand the current dogma

102 two ligands associated with diabetes, induce NIK in islets.

103 ow that TRAF1 depletion prevents TNF-induced NIK stabilization and reduces p52 production.

104 In addition, mice with induced NIK deletion exhibit a significant decrease in germinal

105 Intestinal NIK signaling modulates M-cell differentiation and elici

106 Importantly, intestinal NIK signaling is active in mouse models of colitis and p

107 njection of a recombinant ICOSL protein into NIK-deficient mice largely rescues their defect in Tfh c

108 Mice with constitutive beta cell-intrinsic NIK activation present impaired insulin secretion with D

109 an spontaneously immortalized keratinocytes (NIKs) expressing the early genes from six distinct human

110 degradation of the NF-kappaB-inducing kinase NIK.

111 as the substrate of the noncanonical kinase NIK, the nfkb2 gene product p100, transitions from a mon

112 y conferred dependence on the protein kinase NIK (also called mitogen-activated protein 3 kinase 14 o

113 regulatory importance of the survival kinase NIK (NF-kappaB-inducing kinase) in genetically engineere

114 AF6, which triggered induction of the kinase NIK in CD4(+) T cells and the noncanonical transcription

115 conjunction with stabilization of the kinase NIK induced larger amounts of p52.

116 aB signaling via the serine/threonine kinase NIK (NF-kappaB-inducing kinase) remains unclear.

117 s) by stabilizing NF-kappaB-inducing kinase (NIK) and activating noncanonical NF-kappaB signaling.

118 sed the levels of NF-kappaB-inducing kinase (NIK) and did not activate NF-kappaB in NIK-deficient MEF

119 NF-kappaB-inducing kinase (NIK) and mitogen-activated protein kinase kinase-1 (MEKK

120 ed degradation of NF-kappaB Inducing Kinase (NIK) and repress non-canonical NF-kappaB activation.

121 at directly binds NF-kappaB-inducing kinase (NIK) and stabilizes it from degradation by disrupting it

122 ted activation of NF-kappaB-inducing kinase (NIK) and the transcription factors RelB and p52 directly

123 protein 1 (RIP1), NF-kappaB-inducing kinase (NIK) and themselves, and regulate the assembly of TNFR s

124 way downstream of NF-kappaB-inducing kinase (NIK) and TNF receptor family members including lymphotox

125 tivated B cells (NF-kappaB)-inducing kinase (NIK) as a potential drug target driving NF-kappaB signal

126 lytic cleavage of NF-kappaB-inducing kinase (NIK) at arginine 325.

127 tion required the NF-kappaB-inducing kinase (NIK) but not the IkappaB kinase (IKK) complex components

128 arget nuclear factor kappaB-inducing kinase (NIK) decreased in the absence of a functional LTbetaR, i

129 ic protein kinase NF-kappaB-inducing kinase (NIK) develop a HES-like disease, reflected by progressiv

130 the noncanonical NF-kappaB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo.

131 hough the role of NF-kappaB-inducing kinase (NIK) in immunity is well established, its relevance in c

132 on phosphorylated NF-kappaB-inducing kinase (NIK) in the non-canonical pathway.

133 NF-kappaB-inducing kinase (NIK) is a central component in the non-canonical NF-kapp

134 NF-kappaB inducing kinase (NIK) is a central component of the noncanonical NF-kappa

135 NF-kappaB-inducing kinase (NIK) is a key trigger in the development of liver injury

136 r factor-kappaB (NF-kappaB) inducing kinase (NIK) is a MAP3K that regulates the activation of NF-kapp

137 NF-kappaB-inducing kinase (NIK) is a primary regulator of the noncanonical NF-kappa

138 NF-kappaB-inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-

139 signaling via the NFkappaB-inducing kinase (NIK) is essential for the formation of a fully functiona

140 signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles,

141 tations affecting NF-kappaB-inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40) activ

142 cule inhibitor of NF-kappaB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxi

143 , we found stable NF-kappaB inducing kinase (NIK) protein in several HL cell lines and that NIK shRNA

144 Here we show that NF-kappaB-inducing kinase (NIK), a central component of the noncanonical NF-kappaB

145 factor kappa B (NF-kappaB)-inducing kinase (NIK), a Ser/Thr kinase, as a novel trigger of fatal live

146 r factor-kappaB (NF-kappaB)-inducing kinase (NIK), an action required for the control of NIK-regulate

147 PS1), nuclear factor kappaB-inducing kinase (NIK), cytotoxic T lymphocyte-associated antigen 4 (CTLA4

148 which lack active NF-kappaB-inducing kinase (NIK), show mild osteopetrosis due to the inhibition of o

149 nd its activator, NF-kappaB-inducing kinase (NIK), support the expansion of tumor-initiating cells (T

150 kappaB pathway is NF-kappaB-inducing kinase (NIK), which functions together with a downstream kinase,

151 stability of the NF-kappaB-inducing kinase (NIK), which is kept at low levels basally by a protein c

152 ECs that express NF-kappaB-inducing kinase (NIK), which is pivotal in LTbeta-induced noncanonical NF

153 the noncanonical NF-kappaB-inducing kinase (NIK)-NF-kappaB2 pathway is not well understood in obesit

154 ds on the upstream NFkappaB-inducing kinase (NIK).

155 activated Akt and NF-kappaB-inducing kinase (NIK).

156 by regulating the NF-kappaB-inducing kinase (NIK).

157 a accumulation of NF-kappaB inducing kinase (NIK).

158 ll dependent upon NF-kappaB inducing kinase (NIK).

159 ugh expression of NF-kappaB-inducing kinase (NIK, also known as MAP3K14) is the rate-limiting step in

160 iated protein MIG-15/Nck-interacting kinase (NIK) works with MIG-38 to direct DTC turning as shown by

161 We also report that Nck-interacting kinase (NIK), a MAP4K4, binds and directly phosphorylates the Ar

162 NF-kappaB-inducing kinase [(NIK), MAP3K14] is an essential kinase linking a subset o

163 thway that operates independent of the known NIK substrate IKKalpha.

164 ting NF-kappaB-inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40) activate the alter

165 Therefore, overactivation of liver NIK in obesity promotes hyperglycemia and glucose intole

166 .027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower rel

167 l LTbetaR, it was speculated that an LTbetaR/NIK axis mediated the angiogenetic signals required for

168 ation from endoplasmic reticulum to Rab5+MAC+NIK+ endosomes followed by endosomal NIK-dependent infla

169 subset of TNF receptor superfamily members, NIK becomes stabilized as a result of TRAF3 degradation,

170 Misshapen/NIKs (Nck-interacting kinases)-related kinase (MINK) and

171 TLS(+) tissues contained significantly more NIK(+) ECs and perivascular platelet-derived growth fact

172 Moreover, NIK is required for recruitment of Drp1 to mitochondria,

173 Moreover, NIK/IKK-alpha/NF-kappaB p50/p65 axis mediated the TNF-al

174 Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by fu

175 Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of

176 Dominant-negative NIK blocked RP3-induced NF-kappaB activation and an RP3

177 The knockdown of MEKK-1, but not NIK, inhibited the IL-1beta increase in Caco-2 TJ permea

178 Notably, NIK stabilization was not accompanied by TRAF3 degradati

179 ell populations are normal in the absence of NIK, but the role of NIK during in vivo T cell responses

180 In the absence of NIK, development of Vgamma5(+) dendritic epidermal T cel

181 af3-Traf2 complex and allows accumulation of NIK to initiate ncNFkappaB signaling in activated T cell

182 the costimulation independent activation of NIK in activated T cells and by promoting the 4-1BB-indu

183 lso restricts the constitutive activation of NIK in anti-CD3-activated T cells.

184 upon degradation of TRAF3 and activation of NIK.

185 ated mice containing a conditional allele of NIK.

186 Tissue microarray analysis of NIK expression reveals that dysplastic nevi (n=22), prim

187 (NIK), an action required for the control of NIK-regulated non-canonical NF-kappaB signaling pathway.

188 cIAP1/2-mediated proteasomal degradation of NIK in MM.

189 Constitutive proteosomal degradation of NIK limits NF-kappaB activation in unstimulated cells by

190 1 mediated ubiquitylation and degradation of NIK.

191 Deletion of NIK in adult mice results in decreases in B cell populat

192 an N-terminal deletion mutant (DeltaN324) of NIK, leading to constitutive non-canonical NF-kappaB sig

193 mbined action of competitive displacement of NIK and TRAF degradation halted NIK turnover, and promot

194 , these findings highlight the importance of NIK in tumor pathogenesis and invite new therapeutic str

195 Germline deletion or inactivation of NIK in mice results in the defective development of B ce

196 ngly, disease development was independent of NIK's known function as an IkappaB kinase alpha (IKKalph

197 Whether inhibition of NIK activity by chemical probes ameliorates liver inflam

198 ochondrial dysfunction through inhibition of NIK and Drp1.

199 Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammat

200 responses, and liver-specific inhibition of NIK led to lower glucagon responses and HGP and protecte

201 In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemic

202 Using knockdown of NIK by siRNA we show that in activated CD8 T cells TRAF1

203 Surprisingly, the siRNA induced knockdown of NIK, but not MEKK-1, prevented the TNF-alpha activation

204 that the established downstream mediators of NIK signaling, IkappaB kinase alpha/beta (IKKalpha/beta)

205 normal immune system, including a mixture of NIK KO and WT T cells, and the virus was cleared normall

206 Using a novel conditional mutant of NIK, we could show in vivo that NIK signaling in thymic

207 rsely, hepatocyte-specific overexpression of NIK resulted in higher glucagon responses and HGP.

208 Importantly, the phenotypes of NIK and TAK1 knockdown were similar to those of IKKalpha

209 ormal in the absence of NIK, but the role of NIK during in vivo T cell responses to antigen has been

210 d secondary lymphoid organs, but the role of NIK in adult animals has not been studied.

211 To assess the cell-intrinsic role of NIK in murine T cell function, we generated mixed bone m

212 organogenesis, given the established role of NIK in neovascularization.

213 velopment and B-cell maturation, the role of NIK in regulating T cell functions remains unclear and c

214 postdevelopmental and cell-specific roles of NIK and the noncanonical NF-kappaB pathway in mice.

215 ed NF-kappaB activation via stabilization of NIK.

216 that regardless of the activation status of NIK and the oncogenic events that cause plasma cell mali

217 cytokines, and eosinophilia and survival of NIK-deficient mice could be prevented completely by gene

218 binding motif (IBM) at the amino terminus of NIK.

219 promotes c-IAP1-dependent ubiquitylation of NIK, resulting in optimal NIK turnover to ensure that no

220 istration of B022 protected against not only NIK but also CCl4-induced liver inflammation and injury.

221 ubiquitylation of NIK, resulting in optimal NIK turnover to ensure that noncanonical NF-kappaB signa

222 exclusive activation of the BCR-NF-kappaB or NIK-NF-kappaB pathways in MCL and provide critical insig

223 When we conditionally overexpressed NIK in T cells, mice suffered rapid and fatal autoimmuni

224 or of beta cell function, as pharmacological NIK activation results in impaired glucose-stimulated in

225 versely, genetic ablation of NLRP12 promoted NIK stabilization, RelB nuclear translocation, and incre

226 its interaction with IKKgamma, helps recruit NIK and TAK1 for IKKalpha and IKKbeta activation, respec

227 irm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essen

228 Unlike other known Tfh regulators, NIK acts by controlling the supporting function of B cel

229 he relationship between NF-kappaBeta2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clini

230 NF-kappaBeta2, RelB, NIK and Bcl3 protein expression levels were assessed by

231 lopment of mTECs, because mice lacking RelB, NIK, or IKKalpha, critical components of this pathway, h

232 However, the mechanism releasing NIK from constitutive degradation remains unclear.

233 gered inflammasome assembly does not require NIK.

234 tify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-

235 s were used to knock-down NIK, the resultant NIK-depleted melanoma cell lines exhibited decreased pro

236 letion of Kupffer cells/macrophages reversed NIK-induced liver destruction and death.

237 T cell-specific NIK ablation reduced the frequency of effector/memory-li

238 Internalized MAC stabilize NIK (NF-kappaB [nuclear factor kappa-light-chain-enhance

239 naling mutant (RP3(Y588F)) did not stabilize NIK.

240 gnaling complex induced by MACs to stabilize NIK.

241 s, which recruited activated Akt, stabilized NIK, and led to phosphorylation of IkappaB kinase (IKK)-

242 , 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pa

243 ents, although the small number of surviving NIK KO memory T cells responded to secondary challenge w

244 , we generated transgenic mice with targeted NIK deletion in CD11c(+) cells.

245 rmation of a NIK-Traf3-Traf2 complex targets NIK for degradation.

246 h fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resista

247 ny more LCMV-specific WT memory T cells than NIK KO memory T cells in both the CD4 and the CD8 compar

248 K) protein in several HL cell lines and that NIK shRNA also affected HL cell line viability.

249 We also demonstrate that NIK kinase aberrantly accumulates in DLBCL cells due to

250 for the first time is the demonstration that NIK modulates beta-catenin-mediated transcription to pro

251 significantly expand the current dogma that NIK is predominantly cytosolic and exclusively regulates

252 adiation-resistant tissues, implicating that NIK-deficient immune cells mediate inflammation in a non

253 These data indicate that NIK mediates both beta-catenin and NF-kappaB regulated t

254 s showed stable NIK protein, indicating that NIK and the noncanonical pathway are very prevalent in H

255 s, and the presence of TLSs, indicating that NIK(+) ECs may not only be important orchestrators of ly

256 These studies reveal that NIK contributes a central mechanism for beta cell failur

257 These findings reveal that NIK, and thus probably the noncanonical NF-kappaB pathwa

258 nts in omenta of Nik(-/-) mice revealed that NIK is dispensable for ectopic kidney vascular integrati

259 d immunohistochemical analysis revealed that NIK was almost exclusively expressed by ECs.

260 Our data show that NIK activity in nonhematopoietic cells controls Th2 cell

261 We show that NIK is localized to mitochondria in cancer cell lines, e

262 Here we show that NIK promotes glucagon responses in obesity.

263 In conclusion, our data show that NIK/IKK-alpha/regulates the activation of NF-kappaB p50/

264 al mutant of NIK, we could show in vivo that NIK signaling in thymic epithelial cells is essential fo

265 IAP1 or cIAP2), in which TRAF3 serves as the NIK-binding adapter.

266 Traf3DE8 disrupts the NIK-Traf3-Traf2 complex and allows accumulation of NIK t

267 is critical for MM survival and explains the NIK-independent role of RelB in MM.

268 although IL-7R expression was reduced in the NIK KO CD8 T cells.

269 B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52

270 Furthermore, in the presence of the NIK IBM mutant, we observed an elevated processing of p1

271 the novel identification and function of the NIK IBM, which promotes c-IAP1-dependent ubiquitylation

272 Comparison of the NIK KO and WT CD4 and CD8 T cell responses at 8 d post i

273 Hepatocyte-specific expression of the NIK transgene triggered massive liver inflammation, oxid

274 The structure reveals that the NIK kinase domain assumes an active conformation in the

275 lized in the presence of c-IAP1, whereas the NIK IBM mutant is stable.

276 While the NIK-dependent activation of RelB-p52 in MM has been repo

277 tion of IL-22 production correlated with the NIK-dependent reduction in cMAF protein abundance and th

278 Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, sur

279 Thus, NIK is a new therapeutic target for MCL treatment, parti

280 Thus, NIK may be a promising therapeutic target for melanoma.

281 e TRAF2 recruits c-IAP1/2 and TRAF3 binds to NIK.

282 UPF1 mutations downregulate NMD, leading to NIK-dependent NF-kappaB induction, which contributes to

283 but also NIK stabilization by forming TRAF1.NIK complex.

284 NF-induced TRAF1 expression identified TRAF1.NIK as a central complex linking canonical and non-canon

285 processing, we mathematically modeled TRAF1.NIK as a coupling signaling complex and validated comput

286 signaling complexes, including TRAF2, TRAF3, NIK, IKK1, and IKK2 have been shown to participate in th

287 unstimulated cells by a cIAP1/2:TRAF2:TRAF3:NIK complex.

288 tional studies to demonstrate that wild-type NIK is destabilized in the presence of c-IAP1, whereas t

289 ation in unstimulated cells by the ubiquitin:NIK E3 ligase comprised of subunits TNFR-associated fact

290 indicate the LTbetaR modifies the ubiquitin:NIK E3 ligase, and also acts as an allosteric regulator

291 IAPs specifically recognize and ubiquitylate NIK in the complex.

292 e that RP3 activates classical NF-kappaB via NIK, NEMO and IKKalpha.

293 As expected, when NIK was depleted there was decreased activation of the n

294 in graft-versus-host disease (GVHD), wherein NIK-deficient mouse T cells transferred into MHC class I

295 ght on the long-standing debate over whether NIK is a constitutively active kinase.

296 that under inflammatory conditions in which NIK is activated, Tregs may lose suppressive function an

297 istent with this, B cells from mice in which NIK is acutely deleted fail to respond to BAFF stimulati

298 e activation of the canonical pathway, while NIK regulated the activation of the noncanonical pathway

299 ere observed in IMT samples, consistent with NIK upregulation in these tumors.

300 g protein 3) inflammasome via a Rab5-ZFYVE21-NIK axis and upregulates ICOS-L (inducible costimulator