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 controls alternative NF-kappaB signaling by increasi

5 NIK deficiency attenuates activation of STAT3 and induct

6 NIK depletion also resulted in reduced expression of gen

7 NIK expression is negatively regulated by the full-lengt

8 NIK interacts with the second baculovirus IAP repeat (BI

9 NIK is activated by a broad spectrum of stimuli.

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

11 NIK is often highly expressed in tumor cells, including

12 NIK is the first kinase shown to phosphorylate and incre

13 NIK levels are elevated in pancreatic islets isolated fr

14 NIK mediated the TNF-alpha activation of inhibitory kapp

15 NIK promotes mitochondrial fission, velocity, and direct

16 NIK transgenic Tregs competed poorly with WT Tregs in vi

17 NIK-deficient naive CD4 T cells are attenuated in the di

18 NIK-dependent NF-kappaB activation downstream of several

19 NIK-depleted melanoma cells exhibited downregulation of

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

21 Studies here show that the C. elegans MIG-15 NIK kinase controls multiple aspects of initial Q cell p

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

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

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

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

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

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

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

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

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

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

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

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

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

35 tumor-induced osteolysis in both RelB-/- and NIK-/- mice by using the B16 melanoma model.

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

37 demonstrating that RP3 disrupts normal basal NIK regulation.

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

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

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

41 TRAF2 inhibited cIAP interaction and blocked NIK degradation.

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

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

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 Consistently, NIK knockout mice are resistant to experimental autoimmu

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 The resulting deregulated NIK activity is associated with constitutive noncanonica

54 the ligated LTbetaR competitively displaced NIK from TRAF3.

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

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

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

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

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

60 These findings establish NIK as an important signaling factor that regulates Th17

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

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

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

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

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

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

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

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

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

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

71 ese experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag.

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

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

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

75 cimens revealed strong positive staining for NIK.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

93 ubiquitin ligase complex, which resulted in NIK stabilization and NF-kappaB2-p100 processing.

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

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

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

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

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

99 osphorylation of BCL10, leading to increased NIK phosphorylation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

123 ells by targeting NF-kappaB-inducing kinase (NIK) for ubiquitin-dependent degradation, thus preventin

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

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

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

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

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

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

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

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

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

133 NF-kappaB inducing kinase (NIK) is required for osteoclastogenesis in response to p

134 that nuclear factor kappaB-inducing kinase (NIK) is suppressed through constitutive proteasome-media

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

136 of IKKalpha on the NFkappaB inducing kinase (NIK) phosphorylation sites Ser(176)/Ser(180) and on the

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

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

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

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

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

142 es in KC, phospho-NF-kappaB-inducing kinase (NIK), cytoplasmic NF-kappaB p100, and nuclear NF-kappaB

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

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

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

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

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

148 We show here that NF-kappaB-inducing kinase (NIK), which is known to regulate B-cell maturation and l

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

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

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

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

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

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

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

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

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

158 Nck-interacting kinases (NIK kinases) have been implicated in cell and nuclear mi

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

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

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

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

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

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

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

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

167 The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-can

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

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

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

171 oss-talk" pathway involving the noncanonical NIK.IKKalpha complex downstream of RIG-I.MAVS.

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

173 Notably, NIK stabilization was not accompanied by TRAF3 degradati

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

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

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

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

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

179 upon degradation of TRAF3 and activation of NIK.

180 ated mice containing a conditional allele of NIK.

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

182 egradation of TRAF3 prevented association of NIK with the cIAP1-cIAP2-TRAF2 ubiquitin ligase complex,

183 at deletion of p100 restores the capacity of NIK-deficient osteoclast (OC) precursors to differentiat

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

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

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

187 1 mediated ubiquitylation and degradation of NIK.

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

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

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

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

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

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

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

195 ochondrial dysfunction through inhibition of NIK and Drp1.

196 Inhibition of NIK in T2/5 DKO cells attenuates basal IKK activity and

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

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

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

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

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

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

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

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

205 Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are implicated in hum

206 We show that overexpression of NIK in mouse B lymphocytes amplifies alternative NF-kapp

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

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

214 ed NF-kappaB activation via stabilization of NIK.

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

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

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

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

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

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

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

222 controls, but the absence of either RelB or NIK completely blocked the tumor-induced loss of trabecu

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 otal NIK following CGN, increases in phospho-NIK in the wild type, IKKbeta(-/-) and IKKalpha(-/-) cel

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

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

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

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

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

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

232 Of the three receptors that require NIK for activation of NF-kappaB, only the lymphotoxin-be

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

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

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

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

237 gnaling complex induced by MACs to stabilize NIK.

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

239 , 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pa

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

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

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

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

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

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

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

247 ation experiments not only demonstrated that NIK associated with RIG-I and its downstream adaptor, mi

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

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

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

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

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

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

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

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

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

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

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

259 We further show that NIK mediates synergistic activation of STAT3 by T-cell r

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

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

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

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

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

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

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

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

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

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

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

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

272 To further understand the role of the NIK.IKKalpha pathway, we compared RSV-induced NF-kappaB

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

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

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

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

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

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

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

280 focal images demonstrated no change in total NIK following CGN, increases in phospho-NIK in the wild

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

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

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

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

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

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

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

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

289 IAPs specifically recognize and ubiquitylate NIK in the complex.

290 BAFF-R-dependent manner, whereas uncoupling NIK from TRAF3-mediated control causes maximal p100 proc

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

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

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

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

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

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

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

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

299 r-associated factor 2), which interacts with NIK, and CGN induced phosphorylation of BCL10, leading t

300 ted in Rag2 knockout mice reconstituted with NIK-deficient T cells, confirming a T-cell intrinsic def