ライフサイエンスコーパス: DAPK

1 DAPK as a negative regulator of STAT3 emerges as therape

2 DAPK attenuated STAT3 activity directly by physical inte

3 DAPK is inactive in normal brain tissues, where it is fo

4 DAPK methylation was assessed by methylation-specific po

5 DAPK methylation, IL-10 lack of expression, COX-2 expres

6 DAPK phosphorylates at least one substrate in vitro and

7 DAPK promoter hypermethylation was found in IgM- B cells

8 DAPK suppresses translation in rabbit reticulocyte lysat

9 DAPK-1 and PTRN-1 physically interact in co-immunoprecip

10 DAPK-1 stimulatory peptides attenuate tryptic cleavage o

11 DAPK-1 was used as a model enzyme to develop selective p

12 in which death-associated protein kinase-1 (DAPK) activates zipper-interacting protein kinase (ZIPK)

13 reas no methylation was observed for APAF-1, DAPK, FANCF, FAS, P14, P21, P73, SOCS-3, and SURVIVIN.

14 ation dynamics of 4 TSGs (p15(INK4B), CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marr

15 amily members, including CHK2, CHK1, DAPK-1, DAPK-3, DRAK-1, and AMPK, as Ser(20) kinases.

16 NORE1A (15%), p14ARF (15%), p16INK4a (10%), DAPK (11%) and CRBP1 (9%), but promoter methylation was

17 and the cellular levels of phospho(Ser(308))-DAPK dramatically increase in response to GA treatment.

18 In these studies we have identified a DAPK-interacting protein called DIP-1, which is a novel

19 Mutation of Ser-289 to alanine results in a DAPK mutant with enhanced apoptotic activity, whereas th

20 the mammalian 40S ribosomal protein S6 is a DAPK substrate.

21 has the most highly conserved elements of a DAPK consensus substrate, including a basic core followe

22 as DAPK siRNA knockdown and treatment with a DAPK inhibitor potentiated STAT3 activation, IL-6 mRNA e

23 M-stimulated CaMKK autophosphorylation after DAPK phosphorylation.

24 -1, suggesting that ligand binding can alter DAPK-1 conformation and lock the enzyme onto its substra

25 approach to develop genetic assays to alter DAPK-1-specific activity in vivo.

26 expression of the endogenous DAPK-alpha and DAPK-beta proteins.

27 d the levels of DAPK autophosphorylation and DAPK catalytic activity in response to tumor necrosis fa

28 t in co-immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport.

29 superfamily, including CHK2, AMP kinase, and DAPK-1.

30 esults provide a mechanism by which PP2A and DAPK activities control cell adhesion and anoikis.

31 revealed that methylation at the RASSF1A and DAPK loci, in addition to tumor stage and grade, were as

32 Hypermethylation of MGMT, RASSF1A, and DAPK was significantly lower in primary melanomas (n=20)

33 BRCA1, hMLH1, GSTP1, MGMT, CDH1, TIMP3, and DAPK), each rigorously characterized for association wit

34 Transient expression of an antisense DAPK cDNA or antisense morpholino oligonucleotides in He

35 owing selection in the presence of antisense DAPK cDNA, are more sensitive to tumor necrosis factor-i

36 enes (p16(INK4A), MGMT, GSTP1, RASSF1A, APC, DAPK, RARbeta, CDH1 and CDH13) in 175 primary pediatric

37 phatase 2A (PP2A), ABalphaC and ABdeltaC, as DAPK-interacting proteins.

38 suppressing TNF-induced STAT3 activation as DAPK siRNA knockdown and treatment with a DAPK inhibitor

39 RCC were most frequently methylated at DAPK (24%), MT1G (20%), NORE1A (19%), CDH1 (16%) and MGM

40 sphoinositide 3-kinase inhibitors attenuated DAPK dephosphorylation induced by mitochondrial toxins.

41 etion of either CHIP or DIP1/Mib1 attenuated DAPK degradation.

42 the phospho-acceptor site, creating a better DAPK-1 peptide consensus and demonstrated that the Km fo

43 apoptosis regulatory activities mediated by DAPK are controlled both by phosphorylation status and p

44 nts, and PTRN-1 localization is regulated by DAPK-1.

45 promoter methylation at CASP8, CDH1, CDH13, DAPK, MGMT, NORE1A, p14ARF and RARB2 in primary Wilms' t

46 e superfamily members, including CHK2, CHK1, DAPK-1, DAPK-3, DRAK-1, and AMPK, as Ser(20) kinases.

47 present in many kinases including PIM, CK1, DAPK, and CLK.

48 ponent of the 40S ribosomal subunit complex, DAPK selectively phosphorylates it at serine 235, one of

49 cell carcinoma tumors at BCL2, PTGS2 (COX2), DAPK, CDH1 (ECAD), EDNRB, RASSF1A, RUNX3, TERT, and TIMP

50 ilms' tumours and CASP8, CDH1, CDH13, CRBP1, DAPK, MGMT, MT1G, NORE1A, p16INK4a, SDHB and RARB2 in pr

51 ooth muscle cells demonstrate that decreased DAPK expression promotes a spontaneous, caspase-mediated

52 hese phosphatase holoenzymes dephosphorylate DAPK at Ser-308 in vitro and in vivo resulting in enhanc

53 oreover, concomitantly to dephosphorylation, DAPK is proteolytically processed by cathepsin after isc

54 The mRNA encoding DAPK is widely distributed and detected in mouse embryos

55 o down-regulate expression of the endogenous DAPK-alpha and DAPK-beta proteins.

56 n experiments are consistent with endogenous DAPK being associated with endogenous S6 in rat brain.

57 acting protein (CHIP) or DIP1/Mib1, enhanced DAPK degradation, and conversely, short interfering RNA

58 Accordingly, epithelial DAPK expression was enhanced in STAT3(IEC-KO) mice.

59 the N1347S mutation strikingly prevented ERK:DAPK-1-dependent apoptosis as defined by poly(ADP-ribose

60 izes DAPK-1 binding to ERK, and prevents ERK:DAPK-1-dependent apoptosis.

61 First, DAPK-interacting proteins were detected in yeast two-hyb

62 P-3, 25% for p16INK4a, 21% for MGMT, 19% for DAPK, 18% for ECAD, 8% for p14ARF, and 7% for GSTP1, whe

63 ta, 11% for GSTP1, 7% for p16(INK4A), 4% for DAPK, and 2% for MGMT.

64 An enzyme assay for DAPK was developed and used to measure activity in adult

65 rine 235 matches the established pattern for DAPK peptide and protein substrates.

66 wed methylation for p16 and 17% the same for DAPK, whereas only 6% of the samples displayed methylati

67 onic fibroblasts and neurons exhibit greater DAPK activity and increased sensitivity to cell death st

68 ted in cancer (p16(INK4A), APC, MGMT, GSTP1, DAPK, CDH1, CDH13, RARbeta and FHIT) in 24 primary TGCTs

69 ically, the signature of a miR-103/107 high, DAPK low, and KLF4 low expression profile correlated wit

70 However, DAPK has not been characterized as an enzyme due to the

71 identical to the previously described human DAPK, and it has a kinase domain and calmodulin-binding

72 on of DAPK-alpha, the mouse homolog of human DAPK has a negligible effect on tumor necrosis factor (T

73 existence of the alternatively spliced human DAPK-beta, and we examined the levels of DAPK autophosph

74 The decline in DAPK expression is paralleled with increased caspase act

75 in kinase activity followed by a decrease in DAPK expression and activity.

76 inactivation of STAT3 led to an increase in DAPK mRNA and protein levels.

77 d Ser-289 as a novel phosphorylation site in DAPK, which is regulated by RSK.

78 re a panel of peptide ligands for testing in DAPK binding and phosphorylation assays.

79 observed following expression of an inactive DAPK S308E mutant.

80 GA-induced DAPK degradation is also dependent on phosphorylation of

81 almodulin-binding domain at Ser-308 inhibits DAPK catalytic activity.

82 DANGER binds directly to DAPK and inhibits DAPK catalytic activity.

83 conservation in the hydrophobic part of its DAPK-1 consensus site.

84 though the expression of the encoded 160-kDa DAPK protein is more restricted.

85 how that the death-associated protein kinase DAPK-1 acts as a negative regulator of wound closure.

86 (34%), and death-associated protein kinase (DAPK) (19%).

87 silencing of death-activated protein kinase (DAPK) abrogated EFS-induced GLUT4 but not CD36 transloca

88 tivation of death associated protein kinase (DAPK) and consequently zipper-interacting protein kinase

89 of the p16, death-associated protein kinase (DAPK) and glutathione S-transferase P1 (GSTP1) genes usi

90 suppressors death-associated protein kinase (DAPK) and Kruppel-like factor 4 (KLF4) in CRC cells, res

91 nflammatory death-associated protein kinase (DAPK) and low levels of pSTAT3.

92 tivation of death-associated protein kinase (DAPK) and the role of lysosome in neuroblastoma cells (S

93 part of the death-associated protein kinase (DAPK) family and belongs to the so-called dark kinome.

94 mbers of the death-activated protein kinase (DAPK) family, an enzyme family of no known direct link t

95 Death-associated protein kinase (DAPK) has been found associated with HSP90, and inhibiti

96 Death-associated protein kinase (DAPK) has been found to be induced by IFN, but its antiv

97 Death-associated protein kinase (DAPK) has been implicated in apoptosis and tumor suppres

98 f the mouse death-associated protein kinase (DAPK) have been identified and their roles in apoptosis

99 Death-associated protein kinase (DAPK) is a calcium calmodulin-regulated serine/threonine

100 Death-associated protein kinase (DAPK) is a calmodulin (CaM)-regulated protein kinase and

101 Death-associated protein kinase (DAPK) is a key player in multiple cell death signaling p

102 Death-associated protein kinase (DAPK) is a multi-domain Ser/Thr protein kinase with an i

103 Death-associated protein kinase (DAPK) is a multidomain calcium/calmodulin (CaM)-dependen

104 Death-associated protein kinase (DAPK) is a pro-apoptotic, calcium/calmodulin-regulated p

105 tivation of death-associated protein kinase (DAPK) occurs via dephosphorylation of Ser-308 and subseq

106 requency of death-associated protein kinase (DAPK) promoter hypermethylation has been noted in B-cell

107 ase (MGMT), death-associated protein kinase (DAPK), E-cadherin (ECAD), p14ARF, and glutathione S-tran

108 suppressor, death-associated protein kinase (DAPK), is a Ca(2+)/calmodulin-regulated Ser/Thr kinase w

109 C. elegans, death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immuni

110 Ser(77) by death-associated protein kinases DAPK and ZIPK.

111 Death-associated protein kinases (DAPK) are serine/threonine protein kinases that have an

112 Full-length DAPK-1 encoding the N1347S mutation was attenuated in tu

113 Full-length DAPK-1 protein harboring a N1347S mutation in the death

114 In the final model, DAPK methylation and IL-10 lack of expression were signi

115 ta distinguishes it from the human and mouse DAPK-alpha.

116 s of TNF-treated cell lines expressing mouse DAPK-beta suggests that the cytoprotective effect of DAP

117 The mouse DAPK-alpha sequence is 95% identical to the previously d

118 These results suggest that the mouse DAPK-beta is a negative regulator of TNF-induced apoptos

119 These data highlight a naturally occurring DAPK-1 mutation that alters the oligomeric structure of

120 The activation of DAPK and signaling pathways were determined using immuno

121 Dephosphorylation and activation of DAPK are shown to temporally precede its subsequent degr

122 Finally, activation of DAPK by PP2A was found to be required for ceramide-induc

123 demonstrate that the cellular activities of DAPK are critical for antagonizing caspase-dependent apo

124 the suppression of the apoptotic activity of DAPK.

125 ivo resulting in enhanced kinase activity of DAPK.

126 atory peptides attenuate tryptic cleavage of DAPK-1, suggesting that ligand binding can alter DAPK-1

127 nded to determine whether the degradation of DAPK in the absence of HSP90 activity is dependent on th

128 th geldanamycin (GA) leads to degradation of DAPK, and this degradation is attenuated by the proteaso

129 ivity and proteasome-mediated degradation of DAPK.

130 st, MK-801, inhibit the dephosphorylation of DAPK after in vitro ischemia.

131 1347S) was identified in the death domain of DAPK-1.

132 miR-103/107-mediated downregulation of DAPK and KLF4 also enabled the colonization of CRC cells

133 a suggests that the cytoprotective effect of DAPK is mediated through both intrinsic and extrinsic ap

134 gesting mTOR may be a downstream effector of DAPK.

135 Peg-IFN-alpha up-regulated the expression of DAPK and mTOR, which was associated with the suppression

136 -demethoxygeldanamycin reduced expression of DAPK.

137 llary RCC demonstrated a higher frequency of DAPK methylation (43%) than clear cell tumours (19%) (P=

138 We identified a new function of DAPK in suppressing TNF-induced STAT3 activation as DAPK

139 s antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis.

140 Inhibition of DAPK and ZIPK facilitates cell restoration to the basal

141 lts uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance o

142 More importantly, knockdown of DAPK or mTOR significantly mitigated the inhibitory effe

143 In addition, knockdown of DAPK reduced the expression of mTOR in peg-IFN-alpha-tre

144 man DAPK-beta, and we examined the levels of DAPK autophosphorylation and DAPK catalytic activity in

145 al HeLa cell lines with attenuated levels of DAPK expression, obtained following selection in the pre

146 Low levels of DAPK promoter hypermethylation, ranging from 0.003 to 1.

147 Loss of DAPK-1 function results in constitutive formation of sca

148 In dissecting the mechanism of DAPK-1 control, a novel mutation (N1347S) was identified

149 04, Fisher's exact test), and methylation of DAPK was detected more frequently in older patients than

150 e results indicate that strict modulation of DAPK activities is critical for regulation of apoptosis

151 Mutagenesis of DAPK catalytic domain at amino acids conserved among pro

152 Overexpression of DAPK enhanced mTOR expression and then inhibited HCV rep

153 Overexpression of DAPK-1 represses innate immune responses to needle wound

154 Overexpression of DAPK-alpha, the mouse homolog of human DAPK has a neglig

155 Overexpression of DAPK-beta has a strong cytoprotective effect on TNF-trea

156 tion is also dependent on phosphorylation of DAPK at Ser(308), and the cellular levels of phospho(Ser

157 suggest that RSK-mediated phosphorylation of DAPK is a unique mechanism for suppressing the proapopto

158 to obtain knowledge about the preferences of DAPK for phosphorylation site sequences.

159 ts, which were suppressed by reexpression of DAPK or KLF4.

160 into substrate preferences and regulation of DAPK, provide a foundation for proteomic investigations

161 cate that miR-103/107-mediated repression of DAPK and KLF4 promotes metastasis in CRC, and this regul

162 PK and mTOR, we further assessed the role of DAPK and mTOR in the peg-IFN-alpha-induced suppression o

163 The role of DAPK as a sensor of mitochondrial membrane potential in

164 the potential profound physiological role of DAPK in neuronal function and pathophysiology, the endog

165 ase and provide evidence for a novel role of DAPK in the regulation of translation.

166 The prognostic roles of DAPK methylation, IL-10, and other biomarkers in NSCLC m

167 of neuroblastoma cells with a stimulator of DAPK reduces protein synthesis.

168 Therefore, we determined the structure of DAPK catalytic domain, used a homology model of docked p

169 being a potential physiological substrate of DAPK.

170 esidue extension of the carboxyl terminus of DAPK-beta distinguishes it from the human and mouse DAPK

171 on status of p16 was correlated with that of DAPK (P = 0.04, Fisher's exact test).

172 founding factors in tumor detection based on DAPK hypermethylation.

173 , whereas silencing of mTOR had no effect on DAPK expression, suggesting mTOR may be a downstream eff

174 kinases in vivo has shown that only CHK1 or DAPK-1 can stimulate p53 transactivation and induce Ser(

175 he presence of hypoxia, thereby potentiating DAPK and KLF4 downregulation and hypoxia-induced motilit

176 associations between methylation of RASSF1A, DAPK and CDH1 in individual tumours.

177 In contrast, HeLa cells with reduced DAPK expression are moderately resistant to cell death i

178 c activity of PP2A also negatively regulates DAPK levels by enhancing proteasome-mediated degradation

179 noprecipitation showed that STAT3 restricted DAPK expression by promoter binding, thereby reinforcing

180 Consistent with these results, DAPK is found in two distinct immune complexes, one cont

181 , we present a novel contraction-induced ROS-DAPK-PKD1 pathway in cardiomyocytes.

182 Furthermore, a selective DAPK inhibitor is neuroprotective in both in vitro and i

183 By silencing DAPK and mTOR, we further assessed the role of DAPK and

184 structure of the death domain, de-stabilizes DAPK-1 binding to ERK, and prevents ERK:DAPK-1-dependent

185 e ligands did, however, strikingly stimulate DAPK activity toward p53, a substrate that shows conserv

186 x, activation of calcineurin, and subsequent DAPK dephosphorylation.

187 n vitro ubiquitination assays confirmed that DAPK is targeted for ubiquitination by both CHIP and DIP

188 We demonstrate that DAPK is a novel target of p90 ribosomal S6 kinases (RSK)

189 These results demonstrate that DAPK is a S6 kinase and provide evidence for a novel rol

190 These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitinatio

191 +, and IgG- subpopulations demonstrated that DAPK hypermethylation was predominantly present in the I

192 using purified components demonstrated that DAPK phosphorylates CaMKK with a stoichiometry of nearly

193 eens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regu

194 It was found that DAPK is rapidly dephosphorylated in response to tumor ne

195 These results indicate that DAPK plays a key role in mediating ischemic neuronal inj

196 This indicates that DAPK could be activated by NMDA receptor-mediated calciu

197 We report that DAPK is regulated by DANGER, a partial MAB-21 domain-con

198 Here, we show that DAPK is phosphorylated upon activation of the Ras-extrac

199 In situ hybridization experiments show that DAPK mRNA expression is up-regulated in brain following

200 onsistent with previous studies showing that DAPK has a role in promoting caspase-independent cell de

201 These data suggest that DAPK-1 binding ligands can be generated to elevate its s

202 This model suggests that DAPK-induced conformational changes in the STAT3 dimer m

203 e relationship between peg-IFN-alpha and the DAPK-mammalian target of rapamycin (mTOR) pathways.

204 ine L13a is phosphorylated at Ser(77) by the DAPK-ZIPK cascade, but EPRS is phosphorylated only at Se

205 al a previously undescribed function for the DAPK tumor suppressor family in regulation of epithelial

206 properties of the open reading frame of the DAPK cDNA.

207 We examined whether a nuclear member of the DAPK family named DAPK3 or ZIP kinase had direct links t

208 The expression of the other members of the DAPK family occurred independently of C/EBP-beta.

209 ients, MSP amplification of a portion of the DAPK promoter followed by PCR product sequencing confirm

210 In conclusion, our data suggest that the DAPK-mTOR pathway is critical for anti-HCV effects of pe

211 Thus, the DAPK-ZIPK-L13a axis forms a unique regulatory module tha

212 SF1A in Wilms' tumour and at RASSF1A, TIMP3, DAPK, SLIT2, MT1G and GSTP1 in RCC.

213 ived peptide fragments were found to bind to DAPK; however, these had no stimulatory effect on its ac

214 DANGER binds directly to DAPK and inhibits DAPK catalytic activity.

215 mitochondrial membrane potential leading to DAPK dephosphorylation and activation.

216 nd their sensitivity is inversely related to DAPK expression.

217 conserved among protein kinases or unique to DAPK provided a link between structure and activity.

218 Overexpression of wild type DAPK induces cell rounding and detachment in HEK293 cell

219 er proportion of B cells (1.074-6.026%) were DAPK hypermethylated than were T cells, monocytes, or ne

220 Therefore, we investigated whether DAPK plays a role in the pegylated IFN-alpha (peg-IFN-al

221 IP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal deg

222 of this kinase and the mechanisms via which DAPK elicits its biological action remain largely unknow

223 Normal circulating lymphocytes with DAPK promoter hypermethylation may act as confounding fa