ライフサイエンスコーパス: ASK1

1 ASK1 directly phosphorylates Daxx at Ser(176) and Ser(18

2 ASK1 forms a high molecular mass complex whose activity

3 ASK1 is a central mediator of oxidant injury, but while

4 ASK1 is essential for the assembly and function of the I

5 ASK1 knockdown in C17.2 neural stem cells diminished hig

6 ASK1 participated in the IRE1alpha signalosome, and remo

7 ASK1 phosphorylation of Daxx, an ASK1 activator protein,

8 ASK1 transgenic mice exhibited no induction of cardiac h

9 ASK1 variants may increase susceptibility to type 2 diab

10 ASK1-interacting protein-1 (AIP1), a recently identified

11 ASK1-JNK signaling promoted phosphorylation of the UPR-a

12 ASK1-TBD is a monomeric and rigid domain that forms a st

13 Apoptosis signal-regulating kinase 1 (ASK1) activation in glomerular and tubular cells resulti

14 lating apoptosis signal-regulating kinase 1 (ASK1) activity and subsequent ASK1-dependent apoptosis.

15 cade involving apoptosis signaling kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK).

16 luding apoptosis signal-regulating kinase 1 (ASK1) and cyclic AMP (cAMP) response element-binding pro

17 O, via Apoptosis Signal-regulating Kinase 1 (ASK1) and Jun-N-terminal Kinase (JNK).

18 d with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP(+)-induced stimulati

19 tified apoptosis signal-regulating kinase 1 (ASK1) as a critical downstream target of HSP27 conferrin

20 w that apoptosis signal-regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells because A

21 ion of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key process in the progression

22 known apoptosis signal-regulating kinase 1 (ASK1) inhibitor bound to its kinase domain led to the de

23 teine, apoptosis signal-regulating kinase 1 (ASK1) inhibitor thioredoxin, and c-Jun NH2-terminal kina

24 Apoptosis signal-regulating kinase 1 (ASK1) is a key regulatory kinase in the proapoptotic res

25 Apoptosis signal-regulating kinase 1 (ASK1) is a Mitogen-Activated Protein Kinase Kinase Kinas

26 Apoptosis signal-regulating kinase 1 (ASK1) is a serine/threonine kinase that responds to a pl

27 Apoptosis signal-regulating kinase 1 (ASK1) is activated by various stresses.

28 e that apoptosis signal regulating kinase 1 (ASK1) may influence in vivo insulin action in Pima India

29 d that apoptosis signal-regulating kinase 1 (ASK1) regulates the late phase of APAP-induced JNK activ

30 in for apoptosis signal-regulating kinase 1 (ASK1) which activates c-Jun NH2-terminal kinase (JNK) an

31 nus of apoptosis signal-regulating kinase 1 (ASK1), a kinase believed to be involved in the pathogene

32 Apoptosis signaling kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase,

33 Apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase,

34 PAK1), apoptosis signal-regulating kinase 1 (ASK1), and polo-like kinase 3 (PLK3).

35 K) and apoptosis signal-regulating kinase 1 (ASK1), unveiling a critical node at the junction of surv

36 own as apoptosis signal-regulating kinase 1 (ASK1).

37 Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-act

38 by an apoptosis signal-regulating kinase 1 (ASK1; MAPKKK) inhibitor and by a p38 inhibitor, indicati

39 while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex.

40 h at the level of apoptotic signal kinase-1 (ASK1) within the IRE1 pathway but without directly inhib

41 CaMKII, TIR-1/SARM adaptor protein and NSY-1/ASK1 MAPKKK, is localized to postsynaptic sites in the A

42 timulation promotes the formation of a Raf-1/ASK1 complex at the mitochondria, inhibits ASK1 kinase a

43 ne the linkage disequilibrium pattern across ASK1 in Pima Indians.

44 and that accumulated Daxx further activates ASK1.

45 esults indicate that Daxx not only activates ASK1 but also is a downstream target of ASK1 and that ac

46 endoplasmic reticulum (ER) stress activates ASK1-JNK signaling cascade, we investigated the role of

47 independent apoptosis pathway by activating ASK1, JNK, and caspase-3.

48 riggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival

49 ed with dominant negative constructs against ASK1, and pharmacologic inhibition of JNK with SP600125

50 Although ASK1 overexpression did not alter the cardiac hypertroph

51 ASK1 phosphorylation of Daxx, an ASK1 activator protein, increases Daxx accumulation in c

52 ccumulation and enhanced inflammation, in an ASK1-dependent manner.

53 on of S58 releases ASK1 from 14-3-3zeta, and ASK1 then activates stress-activated protein kinases, le

54 pression resulted in PI3K-Akt activation and ASK1-JNK inactivation leading to accelerated PCa growth

55 proteins stimulate ASK1 kinase activity and ASK1-dependent apoptosis.

56 zed in 536 nondiabetic Native Americans, and ASK1 expression was examined in skeletal muscle of 153 n

57 ma enhanced the association between JAK2 and ASK1, and the ASK1-JAK2 complex was labile and was stabi

58 ed key arrestin-binding elements in JNK3 and ASK1 and investigated the molecular interactions of arre

59 rate arrestins interact with JNK3, MKK4, and ASK1, but only arrestin3 facilitates JNK3 activation.

60 eviously shown to bind JNK3alpha2, MKK4, and ASK1.

61 that this peptide also binds MKK4, MKK7, and ASK1, which are upstream JNK3-activating kinases.

62 Our results also suggest that PRX2 and ASK1 may be potential targets for neuroprotective interv

63 proteins upon OTA treatment in scrambled and ASK1 knockdown cells, respectively.

64 on of the MAP2K MEK6 by two MAP3Ks, TAO2 and ASK1, and the subsequent phosphorylation of p38alpha by

65 pendent manner to block DAXX trafficking and ASK1-JNK activation.

66 rization of the TRX1-binding domain of ASK1 (ASK1-TBD) and its complex with reduced TRX1.

67 inding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding.

68 ributes to apoptosis of plasma cells because ASK1 activity was induced during differentiation of shor

69 CR identified a positive correlation between ASK1 expression in skeletal muscle biopsies and in vivo

70 The link between ASK1 activation and endoplasmic reticulum (ER) stress, t

71 und that the KNC mutant, which tightly binds ASK1, MKK4, and JNK3 without facilitating JNK3 phosphory

72 for the first time ARC-DAXX binding to block ASK1-JNK activation as an ARC-specific endogenous mechan

73 PTP/MPP(+)-induced neurotoxicity by blocking ASK1-mediated signaling.

74 Because both ASK1 and ANP are associated with pathologic cardiac hype

75 ival in normal and malignant plasma cells by ASK1.

76 ocessivity in the phosphorylation of MEK6 by ASK1, and suggested that the order of phosphorylation is

77 rt-lived plasma cells, and, when produced by ASK1-deficient mice, these cells survived better than th

78 am regulatory kinase of the MKK/JNK cascade, ASK1, Hsp27 effectively inhibited ASK1 activity via a ph

79 ith the components of the two MAPK cascades, ASK1-MKK4-JNK3 and c-Raf-1-MEK1-ERK2.

80 When expressed in HEK293T cells, ASK1 was reproducibly purified within a high-molecular m

81 py shows that, when expressed in Hela cells, ASK1 and NPPA exhibit distinct, but overlapping, stainin

82 In malignant plasma cells, ASK1 transcription was directly suppressed by B lymphocy

83 t accumulation and interaction with cellular ASK1.

84 nctionally, TAT.ARC treatment inhibited DAXX-ASK1-JNK signaling in the ischemic brain.

85 Thus, the Daxx-ASK1 positive feedback loop amplifying JNK/p38 signaling

86 t wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine pho

87 ression in HK-2 cells successfully decreased ASK1, which was confirmed by Western blot analysis.

88 directly interacts with and deubiquitinates ASK1 in hepatocytes.

89 Knocking down ASK1 inhibits ionomycin-induced p38 phosphorylation and

90 was neuroprotective and inhibited downstream ASK1 signaling pathways.

91 odulating the redox status of the endogenous ASK1 inhibitor thioredoxin (Trx).

92 an suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis, whereas loss

93 4-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling.

94 thioredoxin binding protein, which enhanced ASK1 activation by disrupting the thioredoxin-ASK1 compl

95 x accumulation in cells and further enhances ASK1 activity through a positive feedback mechanism.

96 xx deficient in polyubiquitin still exhibits ASK1-dependent accumulation and interaction with cellula

97 ckstrin homology domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding

98 que molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

99 ducing Trx2 binding to ASK1 and allowing for ASK1 phosphorylation/activation, resulting in induction

100 in and an intact TPR region are required for ASK1 activity.

101 However, the phosphatase(s) responsible for ASK1 dephosphorylation at pSer967 has not been identifie

102 e findings demonstrate an essential role for ASK1 in cell death induced by ER stress.

103 ative stress, suggesting a possible role for ASK1 in diabetic nephropathy.

104 K2 S964A-induced dissociation of 14-3-3 from ASK1 correlated with enhanced phosphorylation of ASK1 at

105 ge, thereby preventing its dissociation from ASK1.

106 Murine embryonic fibroblasts from ASK1 knock-out mice, alveolar epithelial cells transfect

107 on was increased in ATII cells isolated from ASK1 knockout mice.

108 pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling.

109 ally inactive mutant, dissociated SOCS1 from ASK1.

110 In conclusion, this study identifies ASK1 as a new therapeutic target in diabetic nephropathy

111 lvement of ASK1 in diverse diseases, the IKK/ASK1 interface offers a promising target for therapeutic

112 lls generated by immunization accumulated in ASK1-deficient mice, suggesting ASK1 also plays a negati

113 ddition to the critical role of C2 domain in ASK1 activity, are important for modulating PI3K-Akt act

114 mediated by a MAP kinase cascade, including ASK1 and c-Jun N-terminal kinase.

115 gest that oxidative stress rapidly increases ASK1 catalytic efficiency for MKK6 phosphorylation by in

116 Indeed, ASK1 transgenic mice showed a greater than 2-fold increa

117 P1) transduces tumor necrosis factor-induced ASK1-JNK signaling.

118 IFN-gamma-induced ASK1 Tyr(P)-718 was enhanced in mouse EC deficient in SH

119 PRX2 inhibited 6-OHDA-induced ASK1 activation by modulating the redox status of the en

120 d the regulation of oxidative stress-induced ASK1-catalyzed phosphorylation of MKK6.

121 active mutant of SHP2 inhibited, TNF-induced ASK1 dephosphorylation.

122 AIP1 at Ser604, are critical for TNF-induced ASK1 dephosphorylation.

123 s-induced, but not oxidative stress-induced, ASK1-JNK activation and cell apoptosis.

124 K cascade, ASK1, Hsp27 effectively inhibited ASK1 activity via a physical association through its N-t

125 1 phosphorylation of ASK1 on Ser83 inhibited ASK1-mediated c-Jun N-terminal kinase phosphorylation as

126 1/ASK1 complex at the mitochondria, inhibits ASK1 kinase activity, and protects ECs from genotoxic st

127 provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a

128 ineage kinase 3 (MLK3) mediates the initial, ASK1-independent phase of APAP-induced JNK activation an

129 Moreover, depletion of intracellular ASK1 reduces the level of AGP-induced oxidative stress a

130 -stress-induced cell death via the IRE1alpha-ASK1-JNK pathway.

131 egulatory region actively primes MKK6, a key ASK1 substrate, for phosphorylation.

132 d activation of the oxidant-sensitive kinase ASK1 and its downstream kinase JNK.

133 ssion of apoptosis signal-regulating kinase (ASK1)-dependent activation of the c-Jun N-terminal kinas

134 inactivation of apoptosis-stimulated kinase (ASK1)-JNK pathways is often detected.

135 e regulation of the stress-activated kinase, ASK1.

136 ct cells upon expression of upstream kinases ASK1, MKK4, or MKK7.

137 Apoptosis signal-regulating kinases (ASK1-3) are apical kinases of the p38 and JNK MAP kinase

138 a well-characterized Arabidopsis Skp1-Like1 (ASK1) Ds insertion allele, ask1, in different Arabidopsi

139 nsgene driven by the ARABIDOPSIS SKP1-LIKE1 (ASK1) promoter and the other CYCA1;2/TAM-GFP driven by t

140 lele for rs1570056 was associated with lower ASK1 expression (P = 0.003, r = -0.22).

141 nhibits the MAP kinase kinase kinase Map3k5 (ASK1) is upstream of JNK1 activation.

142 In contrast, proteins modulating ASK1 activity and degradation were found to interact wit

143 Genetic variants in or near ASK1 were analyzed to assess the role of this gene in in

144 reviously we have shown that tyrosine 718 of ASK1 when phosphorylated is critical for SOCS1 binding a

145 ds enhanced phosphorylation of serine 967 of ASK1, promoting ASK1 binding to 14-3-3, an event associa

146 ll death through IRE1-mediated activation of ASK1 and possibly downstream caspases.

147 In turn, activation of ASK1 is associated with a number of human pathological c

148 eine also inhibits AGP-induced activation of ASK1, as well as apoptosis.

149 results in an increase in the activation of ASK1, JNK, and caspase 3 along with exacerbation of 4-HN

150 deficient Jurkat cells via the activation of ASK1, JNK, and caspase 3, and the apoptosis can be inhib

151 xx and inhibits Daxx-dependent activation of ASK1, prevents Daxx phosphorylation and stabilization.

152 2A-AIP1 complex in TNF-induced activation of ASK1-JNK apoptotic signaling.

153 and AIP1 cooperatively induce activation of ASK1-JNK signaling and EC apoptosis, as demonstrated by

154 tion of ASK1 at Tyr(P)-718 and activation of ASK1-JNK signaling, as well as EC apoptosis, are signifi

155 y in renal epithelial cells by activation of ASK1.

156 ctor-alpha (TNF-alpha)-induced activation of ASK1.

157 The activity of ASK1 is triggered by various stress stimuli and is invol

158 t directly inhibiting the kinase activity of ASK1 or >400 other kinases tested.

159 ronounced when a dominant-negative allele of ASK1 with deficient kinase activity was coexpressed with

160 aft animal model; furthermore, alteration of ASK1 activity affected MM cell survival.

161 n of ASK2 dramatically reduced the amount of ASK1 complexed with 14-3-3.

162 r-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.

163 Importantly, the strength of the binding of ASK1 or JNK3, as revealed by the efficiency of co-immuno

164 a dominant role of ASK2 in 14-3-3 control of ASK1 function.

165 ron-gamma (IFN-gamma) induced degradation of ASK1 in normal but not in SOCS1-KO endothelial cells (EC

166 S1 binding and SOCS1-mediated degradation of ASK1.

167 The evidence for TNF-signaling dependence of ASK1-mediated apoptosis suggests possible mechanisms for

168 ein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK

169 necrosis factor-induced dephosphorylation of ASK1 at Tyr(P)-718 and activation of ASK1-JNK signaling,

170 for phosphorylation and dephosphorylation of ASK1 at Tyr-718 are unknown.

171 talytic subunit induced dephosphorylation of ASK1 pSer967 and activation of c-Jun N-terminal kinase (

172 RNA blunted TNF-induced dephosphorylation of ASK1 pSer967 and activation of JNK without effects on NF

173 is factor (TNF)-induced dephosphorylation of ASK1 pSer967 in ECs was blocked by PP2A inhibitor okadai

174 K and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP

175 aracterization of the TRX1-binding domain of ASK1 (ASK1-TBD) and its complex with reduced TRX1.

176 -3-3zeta interacts with the kinase domain of ASK1 in close proximity to its active site, thus indicat

177 s N-terminal domain and the kinase domain of ASK1.

178 The expression of ASK1 and Blimp-1 showed an inverse correlation between n

179 ells), and induction of Bax in the hearts of ASK1 transgenic mice following 1 and 8 weeks of pressure

180 Incubation of ASK1-depleted HK-2 cells with the two FLCs prevented the

181 associated with redox dependent induction of ASK1 and activation of stress kinases p38 and JNK.

182 o prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun

183 Finally, the inhibition of ASK1 by Akt was responsible for the protection from apop

184 The role of 14-3-3 in the inhibition of ASK1 has yet to be elucidated.

185 sly unexplored association and inhibition of ASK1 kinase signaling.

186 ll as the interaction with and inhibition of ASK1 signaling.

187 this study, we performed RNA interference of ASK1 in HEK293 cells and employed an iTRAQ-based quantit

188 Because of the intimate involvement of ASK1 in diverse diseases, the IKK/ASK1 interface offers

189 Moreover, knockdown of ASK1 or inhibition of the ASK1/MKK4 cascade effectively

190 at the catalytic efficiency (k(cat)/K(m)) of ASK1 was 4000-fold greater in cells treated with H(2)O(2

191 ally investigate the regulatory mechanism of ASK1 in OTA-induced renal cytotoxicity.

192 lthough a 14-3-3-binding defective mutant of ASK1 (S967A) has no effect on the ASK2/14-3-3 interactio

193 iac-specific and inducible overexpression of ASK1 in the heart to assess its gain-of-function effect.

194 correlated with enhanced phosphorylation of ASK1 at T838 and increased c-Jun N-terminal kinase phosp

195 ime-dependent increase in phosphorylation of ASK1 at T845, indicating activation of this enzyme, was

196 FN-gamma-induced tyrosine phosphorylation of ASK1 at Tyr-718 was blocked by a JAK2-specific inhibitor

197 Direct phosphorylation of ASK1 by IKK also defines a novel IKK phosphorylation mot

198 her demonstrate that PIM1 phosphorylation of ASK1 decreases its kinase activity induced by oxidative

199 PIM1 phosphorylation of ASK1 on Ser83 inhibited ASK1-mediated c-Jun N-terminal k

200 that regulate inhibitory phosphorylation of ASK1.

201 sphorylation, the two biological readouts of ASK1 activation.

202 eased phosphorylation of endogenous Ser83 of ASK1 and was associated with a decrease in cell viabilit

203 l a compact and slightly asymmetric shape of ASK1-TBD and suggest reduced TRX1 interacts with this do

204 We demonstrated that NPPA is a substrate of ASK1 in an in vitro kinase assay.

205 iated phosphorylation for its suppression of ASK1 cell death signaling and neuroprotection against is

206 3-3, an event associated with suppression of ASK1 function.

207 Suppression of ASK1 is crucial for cell survival because its enforced e

208 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly inte

209 ctionally important endogenous suppressor of ASK1 hyperactivation in the pathogenesis of NASH and ide

210 ates ASK1 but also is a downstream target of ASK1 and that accumulated Daxx further activates ASK1.

211 ulator of S58 phosphorylation and thereby of ASK1-mediated cell death.

212 -regulation of Thioredoxin (Trx)-1 to permit ASK1 activation and apoptosis.

213 t JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of A

214 and decreased association of phosphorylated ASK1 with FAK.

215 ormed a complex with tyrosine-phosphorylated ASK1, suggesting that ASK1 is a direct SHP2 substrate.

216 IKK forms a complex with and phosphorylates ASK1 at a sensor site, Ser967, leading to the recruitmen

217 Here we show that PIM1 phosphorylates ASK1 specifically on serine residue 83 (Ser83) both in v

218 Both analogs are potent ASK1 inhibitors in biochemical and cellular assays (19,

219 the ability of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation.

220 which the central regulatory region promotes ASK1 activity via its pleckstrin homology domain but als

221 phorylation of serine 967 of ASK1, promoting ASK1 binding to 14-3-3, an event associated with suppres

222 uppressor of kinetochore protein 1) protein, ASK1 and ASK2, are required for Agrobacterium-mediated p

223 independent of the Arabidopsis SKP1 protein, ASK1.

224 Groups of diabetic Nos3(-/-) mice received ASK1 inhibitor (GS-444217 delivered in chow) as an early

225 Small interfering RNA designed to reduce ASK1 expression in HK-2 cells successfully decreased ASK

226 y decreasing insulin sensitivity via reduced ASK1 expression.

227 Reducing ASK1 protein expression using small interfering RNA also

228 at JAK2-SOCS1 and SHP2 reciprocally regulate ASK1 phosphorylation and stability in response to cytoki

229 ings identify a novel pathway that regulates ASK1 activation and oxidant stress-induced cell death.

230 Phosphorylation of S58 releases ASK1 from 14-3-3zeta, and ASK1 then activates stress-act

231 d in the IRE1alpha signalosome, and removing ASK1 abrogated the proapoptotic kinase activity of IRE1a

232 this study, we examined whether a selective ASK1 inhibitor can prevent the induction and progression

233 l models identified selonsertib, a selective ASK1 inhibitor, as a potential therapeutic agent.

234 occur through PAR1, reactive oxygen species, ASK1, and JNK signaling in HGFs.

235 ngagement with Sdc1 is blocked by SSTNIGF1R, ASK1 becomes activated, and initiates JNK- and caspase-3

236 as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not MKK7) activation and

237 eterotrimeric G12 and G13 proteins stimulate ASK1 kinase activity and ASK1-dependent apoptosis.

238 In response to oxidative stress, ASK1 activates the cell death-associated p38 MAPK pathwa

239 ssociation of ASK1 with SOCS1 and subsequent ASK1 degradation.

240 ting kinase 1 (ASK1) activity and subsequent ASK1-dependent apoptosis.

241 cumulated in ASK1-deficient mice, suggesting ASK1 also plays a negative role in survival of long-live

242 al-triggered ASK1 activation, and suppresses ASK1-mediated functions.

243 the IGF1 receptor (IGF1R) by Sdc1 suppresses ASK1-dependent apoptosis in multiple myeloma cells.

244 Collectively, we conclude that ASK1 is a predominant Skp1 protein in Arabidopsis and th

245 We concluded that ASK1 plays an essential role in promoting OTA-induced re

246 , which further supports our hypothesis that ASK1 plays a causal role in diabetes-induced ER stress a

247 These results indicate that ASK1 does not directly regulate the cardiac hypertrophic

248 ay classification and analysis revealed that ASK1 participated in OTA-induced inhibition of mRNA spli

249 However, the role that ASK1 plays in regulating the cardiac hypertrophic respon

250 Mechanistically, we show that ASK1 is bound to active IGF1R and inhibited by Tyr and S

251 Here, we show that ASK1-dependent phosphorylation of Daxx induces Lys(63) (

252 Our results showed that ASK1 knockdown alleviated OTA-induced ROS generation and

253 We have previously shown that ASK1-interacting protein 1 (AIP1) transduces tumor necro

254 yrosine-phosphorylated ASK1, suggesting that ASK1 is a direct SHP2 substrate.

255 NPPA in the culture medium, suggesting that ASK1 negatively impacts NPPA processing and/or secretion

256 Reactive oxygen species then activated the ASK1-JNK/p38 pathways.

257 Here, we report that IFN-gamma activates the ASK1-MKK3/MKK6-p38 mitogen-activated protein kinase (MAP

258 e association between JAK2 and ASK1, and the ASK1-JAK2 complex was labile and was stabilized by the p

259 mplex ( approximately 1500 kDa) known as the ASK1 signalosome.

260 ructural analysis of the complex between the ASK1 kinase domain phosphorylated at Ser-966 (pASK1-CD)

261 iption-independent action in controlling the ASK1-JNK axis, coupling IKK to ROS and ER stress respons

262 On the other hand, the ASK1-p38 pathway induced expression of the monocyte chem

263 ere, we report a biochemical analysis of the ASK1 kinase domain in conjunction with its N-terminal th

264 osphorylated Ser-966 motif downstream of the ASK1 kinase domain.

265 ibited the MPP(+)-induced stimulation of the ASK1-mediated signaling cascade.

266 Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signa

267 over, knockdown of ASK1 or inhibition of the ASK1/MKK4 cascade effectively inhibited cell death follo

268 correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with

269 3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4-JNK3 module, promoting JNK3 phosphorylation, w

270 Furthermore, it occurs through the ASK1 pathway and is JNK- and p38-dependent.

271 nals couple ASK2 S964 phosphorylation to the ASK1 signalosome through dual engagement of 14-3-3.

272 degradation were found to interact with the ASK1 signalosome once MKK6 activation was completed.

273 tently, endogenous MKK6 was found within the ASK1 signalosome in intact cells and in addition copurif

274 increasing MKK6 binding affinity within the ASK1 signalosome prior to induction of inactivation and

275 SK1 activation by disrupting the thioredoxin-ASK1 complexes.

276 vate the intrinsic apoptotic pathway through ASK1, JNK, and p53.

277 ces the accumulation of Daxx protein through ASK1 activation by preventing its proteasome-dependent d

278 endent manners, in part by signaling through ASK1 and CREB, and contributes to cancer cell invasion a

279 rexpression or ING3 knockdown in addition to ASK1 knockdown further rescued the increased sensitivity

280 dizes Trx2, thereby reducing Trx2 binding to ASK1 and allowing for ASK1 phosphorylation/activation, r

281 phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 b

282 in vitro and in vivo and that PIM1 binds to ASK1 in cells by co-immunoprecipitation.

283 Whereas AIP1, via its C2 domain, binds to ASK1, PP2A binds to the GAP domain of AIP1.

284 critical role of AIP1 in recruiting PP2A to ASK1.

285 mally induces association of AIP1 with TRAF2-ASK1.

286 14-3-3, counteracts stress signal-triggered ASK1 activation, and suppresses ASK1-mediated functions.

287 1 deficiency augmented cold stress-triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alle

288 vel redox-sensitive mitochondrial TXNIP-Trx2-ASK1 signaling cascade.

289 Additionally, coexpressing wild-type ASK1 with NPPA in Hela cells led to reduced levels of NP

290 However, the mechanism underlying ASK1 activation is still unclear, and thus the endogenou

291 nd HMGB1 translocation (CC1-KO->WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-s

292 We sought to investigate whether ASK1 is involved in the unfolded protein response (UPR)

293 SHP2 associated with ASK1 in response to tumor necrosis factor in EC.

294 hanistically, cardiomyopathy associated with ASK1 overexpression after 8 weeks of pressure overload w

295 intact cells and in addition copurified with ASK1 following treatment for 3 min.

296 In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquit

297 r Daxx accumulation or Daxx interaction with ASK1 because mutant Daxx deficient in polyubiquitin stil

298 e, which forms a positive feedback loop with ASK1 through Txnip.

299 ermore, TNF-induced association of PP2A with ASK1 was diminished in AIP1-knockdown ECs, suggesting a

300 nduces a complex formation of AIP1-PP2A with ASK1.