ライフサイエンスコーパス: neddylation

1 bunit with the ubiquitin-like protein Nedd8 (neddylation).

2 d, sometimes, by ubiquitin enzymes (atypical neddylation).

3 domain, which regulates its E3 activity for neddylation.

4 rane, raises questions about its function in neddylation.

5 through the UB transfer cascade for protein neddylation.

6 east to explore the effects of CIF on cullin neddylation.

7 /Erk pathway, was identified as a target for neddylation.

8 tivity of which is most likely controlled by neddylation.

9 leading to a decrease in steady-state cullin neddylation.

10 ide onto Cullin proteins in a process called neddylation.

11 and genes that are involved in autophagy and neddylation.

12 nces recruitment of Ubc12 to Cul1 to promote neddylation.

13 obic pocket in the E3, Dcn1, promotes cullin neddylation.

14 hat CAND-1 is a negative regulator of cullin neddylation.

15 hat depends on a protein modification termed neddylation.

16 -mediated retinoblastoma degradation and p53 NEDDylation.

17 unneddylated CUL1 and is dissociated by CUL1 neddylation.

18 conjugating enzyme, as a substrate for auto-neddylation.

19 esses is activated by Nedd8 through covalent neddylation.

20 ly conserved gene that functions as an E3 in neddylation.

21 indirect inhibitor of CRL by blocking cullin neddylation.

22 vities of SCCRO and its paralogues in cullin neddylation.

23 MJ formation, possibly by regulation of AChR neddylation.

24 rcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin ne

25 hiometry reveals that, independent of cullin neddylation, a large fraction of cullins are assembled w

26 pe ubiquitination E3 ligases is regulated by neddylation, a process analogous to ubiquitination that

27 Activation of atypical neddylation accumulated a surrogate misfolded protein, G

28 , ATF3, and NAEbeta (the beta-subunit of the neddylation activation enzyme).

29 quitin chains to the UBA domain inhibits the neddylation activity of SCCRO in vivo by inhibiting SCCR

30 ns as a tumor suppressor by antagonizing the neddylation activity of SCCRO.

31 Pharmacologic targeting of neddylation activity with MLN4924 (IC50, 4.7 nM) stabili

32 o apoptosis in clones with a net decrease in neddylation activity.

33 an be effectively modulated by CSN, and that neddylation allows Cul1 to form larger protein complexes

34 Targeting neddylation also suppressed the ability of DCs to stimul

35 ce of adaptor modules, rather than cycles of neddylation and CAND1 binding, drives CRL network organi

36 ing and antagonistic activity that regulates neddylation and cell proliferation activities in vivo.

37 In flies, both dSCCRO and dSCCRO3 promote neddylation and cell proliferation, whereas dSCCRO4 nega

38 SCCRO family members cooperatively regulate neddylation and cell proliferation.

39 g in complete but transient loss of cullin-1 neddylation and consequent effects on NF-kappaB and beta

40 ptors cooperatively provide tight control of neddylation and cullin-RING-ligase activity in vivo.

41 We provide evidence that cullin neddylation and deneddylation is highly dynamic, that it

42 dylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates.

43 n of enzymes and complexes known to regulate neddylation and deneddylation, including the COP9 signal

44 nding to Cul4-DDB1[VprBP] leads to increased neddylation and elevated intrinsic ubiquitin ligase acti

45 conclude that DEN-1 is a regulator of cullin neddylation and fine-tunes the inflammatory response in

46 inhibitor MLN4924 reportedly blocked cullin neddylation and inactivated CRLs, which resulted in apop

47 been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers

48 ion pathway, targeting effector caspases for neddylation and inactivation.

49 to conformational changes in CRLs that allow neddylation and initiation of ubiquitination.

50 s of SCCRO on abscission involve its role in neddylation and localization of Cul3 to the midbody.

51 The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclea

52 we investigated the contribution of Cullin-1 neddylation and NF-kappaB signaling to mucosal inflammat

53 treatment led to rapid inhibition of Cullin1 neddylation and notably suppressed growth and survival a

54 wn of L30 or L29 significantly increased the NEDDylation and nuclear retention of L11.

55 and, to a lesser extent, dSCCRO3 rescue the neddylation and proliferation defects promoted by expres

56 localization of Cul1 accompanying decreased neddylation and proliferation in SCCRO(-/-) mouse embryo

57 d SCCRO4 promote, and human SCCRO3 inhibits, neddylation and proliferation when expressed in flies.

58 data indicate that NUB1L suppresses atypical neddylation and promotes the degradation of misfolded pr

59 dentify SENP8 as a proximal regulator of Cul neddylation and provide an important role for SENP8 in f

60 s the nucleolus as a target of inhibitors of NEDDylation and provides a mechanism for p53 activation

61 er cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and surviva

62 (20-100 nmol/L) effectively inhibited cullin neddylation and sensitized pancreatic cancer cells to io

63 rupt Smurf interaction with Nedd8 reduce its neddylation and stabilize the protein.

64 ggest that parkin and PINK1 are regulated by neddylation and that impaired NEDD8 modification of thes

65 lthough the effects of NUB1 on p53 depend on NEDDylation and the murine double minute 2 (Mdm2) E3-lig

66 These results provide a crucial link between neddylation and transcriptional regulation by SIRT1, a N

67 lyubiquitinated proteins, and have increased neddylation and transformation activities.

68 hibitory effects of SCCRO3 on SCCRO-promoted neddylation and transformation require both an intact my

69 SCCRO/DCUN1D1 plays a key regulatory role in neddylation and, consequently, cullin-RING ligase activi

70 expressed Developmentally Down-regulated 8) (neddylation) and deactivated by NEDD8 removal (deneddyla

71 mediated by NEDD8-specific enzymes (typical neddylation) and, sometimes, by ubiquitin enzymes (atypi

72 Decreased nuclear localization, neddylation, and defective proliferation in SCCRO(-/-) m

73 t with their gene products normally opposing neddylation, and GFP fusions to several suppressors were

74 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12

75 t, the stability of stonin 2 is regulated by neddylation, another CSN-associated activity.

76 tion inhibition reduces fibrosis, suggesting neddylation as a potential and attractive therapeutic ta

77 fold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the

78 ntified a new class of inhibitors of protein neddylation based on the profiles of the UB C-terminal s

79 ation not only isolated the known targets of neddylation but also the constellation of enzymes and co

80 Csn6 haplo-insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to compromise

81 in neddylation) serves as an accessory E3 in neddylation by binding to cullin and Ubc12 to allow effi

82 Inversely, inhibition of NEDDylation by MLN4924 blocked proinflammatory gene expr

83 In contrast, suppression of atypical neddylation by NUB1L overexpression enhanced GFPu degrad

84 Expression of SCCRO3 inhibits SCCRO-promoted neddylation by sequestering cullins to the membrane, the

85 Further dissection of the mechanisms such as neddylation, by which these genes regulate immune respon

86 inally, we have shown that affinity-directed NEDDylation can be applied to two other protein-ligand i

87 Neddylation can be prevented by MLN4924, a drug that inh

88 e COP9 signalosome, Nub1, and enzymes in the neddylation cascade.

89 We provide evidence that augmented neddylation characterizes activated HSCs, suggesting tha

90 on in vivo involving nuclear localization of neddylation components and recruitment and proper positi

91 ting SCCRO-promoted nuclear translocation of neddylation components and results in a corresponding de

92 Thus, blocking neddylation could be a novel strategy for mitigating imm

93 SENP8, a NEDD8-specific protease, but not by neddylation-deficient BCA3 or a SENP8 mutant.

94 ines which ectopically express wild-type and NEDDylation-deficient HBx and found that NEDDylation-def

95 HBx NEDDylation sites and observed that the NEDDylation-deficient HBx has shorter half-life.

96 and NEDDylation-deficient HBx and found that NEDDylation-deficient HBx showed less chromatin localiza

97 CRL activity and demonstrate that the cullin neddylation-deneddylation cycle is not only required to

98 ination in vivo, raising the question of how neddylation/deneddylation exerts its effects.

99 SN is physically recruited to DSB sites in a neddylation-dependent manner, and is required for timely

100 L4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partne

101 bind to p65 and the cyclin D1 promoter in a neddylation-dependent manner.

102 al approaches, and the CULLIN-ASSOCIATED AND NEDDYLATION DISSOCIATED 1 (CAND1) and TRANSPORT INHIBITO

103 ulatory protein CAND1 (cullin associated and neddylation dissociated) are disrupted.

104 psis ortholog of human Cullin Associated and Neddylation-Dissociated (CAND1)/TIP120A, a protein recen

105 erpart of human CAND1 (cullin-associated and neddylation-dissociated) and demonstrate that it can pre

106 activity of SCCRO requires its potentiating neddylation domain, which regulates its E3 activity for

107 Dcn1's "potentiating neddylation" domain (Dcn1(P)) acts as an additional E3,

108 that SCCRO is an important component of the neddylation E3 complex that functions to recruit charged

109 oncogene (SCCRO)/DCUN1D1, a component of the neddylation E3 complex, regulates the activity of the cu

110 In addition, we have been able to improve NEDDylation efficiency through rational mutagenesis.

111 Our results demonstrate that blocking neddylation, either pharmacologically or using siRNA, ab

112 We find that AXR1 as well as other neddylation enzymes are autoneddylated at multiple lysin

113 mily of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts a

114 per elaboration of dendrites and may require neddylation for its proper function.

115 gest family of E3 ligases and require cullin neddylation for their activation.

116 The combined effects of neddylation greatly enhance the probability that a subst

117 Neddylation has an important role in ubiquitin-mediated

118 nized function of the CSN in regulating EGFR neddylation has broad-reaching implications for understa

119 however, physiological regulation of cullin neddylation has not been described in mammalian systems.

120 HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring

121 otoxic stresses induced typical and atypical neddylation in cardiomyocytes.

122 Our results show deregulated neddylation in clinical fibrosis and both in mouse biled

123 in vivo and define conditions for targeting neddylation in models of mucosal inflammation.

124 mined the mechanism and consequences of AXR1 neddylation in more detail.

125 me the inhibitory effects of CAND1 on cullin neddylation in purified protein assays.

126 and augments but is not required for cullin neddylation in reactions using purified recombinant prot

127 Here we investigated the role of protein neddylation in regulating T-cell function using an in vi

128 ecific suppressors partially restored Cullin neddylation in rfl-1(or198ts) mutants, consistent with t

129 d enzymatic function of rapsyn and a role of neddylation in synapse formation, and reveals a potentia

130 hus identifies an important role for protein neddylation in T-cell function, which may serve as a the

131 onse to CG-12, leading to increased cullin 1 neddylation in the Skp1-cullin1-F-box protein complex an

132 suggest that SCCRO has an essential role in neddylation in vivo involving nuclear localization of ne

133 tropic effects that are essential for cullin neddylation in vivo.

134 ant but less understood type of PTM, namely, neddylation, in regulating DC functions.

135 ggests a role for an additional modification-neddylation-in negative regulation of p53 transcriptiona

136 with a nuclear localization sequence allowed neddylation independent of SCCRO, but at a lower level.

137 of EGFR modifications from ubiquitination to neddylation, inhibiting EGFR dynamics in response to an

138 duced apoptosis in mouse hepatocytes whereas neddylation inhibition ameliorated apoptosis through red

139 haracterizes activated HSCs, suggesting that neddylation inhibition could be important for resolving

140 hepatocyte cell death and inflammation after neddylation inhibition could partly account for reductio

141 Indeed, neddylation inhibition in activated HSCs induces apoptos

142 in activated macrophages, were reduced after neddylation inhibition in mouse Kupffer cells.

143 Neddylation inhibition prevented the degradation of inhi

144 Neddylation inhibition reduces fibrosis, suggesting nedd

145 stologic analysis of the colon revealed that neddylation inhibition results in increased tissue damag

146 Importantly, neddylation inhibition, by using the pharmacological inh

147 MLN4924 is a neddylation inhibitor currently under investigation in m

148 Nedd8 silencing or treating cells with the neddylation inhibitor MLN4924 led to diminished caspase-

149 ntestinal epithelial cells revealed that the neddylation inhibitor MLN4924 prominently induces the de

150 Neddylation is a biochemical event associated with diver

151 Neddylation is a post-translational protein modification

152 Neddylation is a posttranslational modification that con

153 Neddylation is a posttranslational modification that pla

154 These studies reveal that intact Cullin-1 neddylation is central to resolution of acute inflammati

155 Neddylation is commonly mediated by NEDD8-specific enzym

156 Although typical neddylation is known to regulate protein function in man

157 Cullin neddylation is modulated by a scaffolding DCN protein th

158 Neddylation is shown to facilitate E3 complex assembly;

159 Neddylation is the conjugation of the molecule neural pr

160 The essential contribution of SCCRO to neddylation is to promote nuclear translocation of the c

161 of ubiquitin-like protein Nedd8 to cullins (neddylation) is essential for the function of cullin-RIN

162 ugation of Nedd8 to a cullin protein, termed neddylation, is an evolutionarily conserved process that

163 he importance of SENP8 in maintaining proper neddylation levels for CRL-dependent proteostasis.

164 bition or depletion of key components of the neddylation machinery concomitantly inhibits stress-indu

165 Therefore, neddylation may also impact survival and proliferation o

166 Pharmacologic inhibition of cullin neddylation may provide a therapeutic opportunity in muc

167 Thus, in plants, neddylation may serve as a regulatory mechanism for cull

168 isms, including acetylation, ubiquitination, neddylation, methylation, and sumoylation.

169 Pharmacological targeting of neddylation (MLN4924) significantly abrogated NF-kappaB

170 e found that the small molecule inhibitor of NEDDylation, MLN4924, alters the morphology and increase

171 Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractiv

172 at CRLs components are up-regulated, whereas neddylation modification is over-activated in a number o

173 Loss of DNA damage-induced neddylation negatively regulated DNA damage-induced foci

174 y showed a time-dependent induction of Cul-1 neddylation, nuclear translocation of NF-kappaB, stabili

175 tinib, we have shown that dasatinib-directed NEDDylation occurs for known endogenous protein binders

176 Neddylation occurs through a multistep enzymatic process

177 mics simulations, we demonstrate that before neddylation occurs, the linker flexibility of Rbx1, a CR

178 g as an adaptor protein that can mediate the neddylation of a non-cullin substrate.

179 PD neurotoxin MPP(+) inhibits neddylation of both parkin and PINK1.

180 se-1 (and CARD) and Nedd8 suggested possible neddylation of caspase-1 CARD.

181 We report that MLN4924 inhibits the neddylation of CRL4, blocking Vpx-induced degradation of

182 ase of p62 and that ATG16L1 is essential for neddylation of Cul-3, a step required for Cul-3 activati

183 Neddylation of CUL1 or the presence of SKP1 and ATP caus

184 Neddylation of Cul3 on Lys 712 is required for Keap1-dep

185 l3Delta9 to the E3 ubiquitin ligase Rbx1 and neddylation of Cul3Delta9 were impaired significantly co

186 e of the DCN1-UBC12 interaction for cellular neddylation of cullin 3.

187 gase type of ubiquitination E3s by promoting neddylation of cullin family members.

188 g Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL.

189 Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degrad

190 CSN6 enhanced neddylation of Cullin-1 and facilitated autoubiquitinati

191 reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effe

192 ement for SCCRO in nuclear translocation and neddylation of cullins in vivo.

193 Our studies indicate that the defective NEDDylation of HBx negatively affects its ability to act

194 on, we revealed that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability and chromati

195 We found that E3 ligase HDM2 promotes NEDDylation of HBx to enhance HBx stability by preventin

196 These results demonstrate that NEDDylation of L11 plays a critical role in mediating p5

197 We show that FBXO11 promotes the neddylation of p53 both in vitro and in vivo.

198 edd8 conjugation to Lys-320 and Lys-321, and neddylation of p53 leads to suppression of p53 function.

199 Neddylation of parkin and PINK1 results in increased E3

200 llular proteins and their activation require neddylation of their cullin subunit.

201 bc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway

202 promoted its degradation through suppressing neddylation of ubiquitinated proteins in cardiomyocytes.

203 ermined that posttranslational modification (neddylation) of Cullin-4 is required for the activation

204 narily conserved, is the NEDD8 modification (neddylation) of cullins, core subunits of the cullin-RIN

205 smaller, and, consequentially, the impact of neddylation on transfer of subsequent ubiquitins by Cdc3

206 ot efficiently bind to Ubc12, promote cullin neddylation, or conform to the reaction processivity par

207 n as DCUN1D1) binds to the components of the neddylation pathway (Cullin-ROC1, Ubc12, and CAND1) and

208 this study provides the first evidence that neddylation pathway is overactive in ccRCC and that MLN4

209 support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assemb

210 HMECs with an intact neddylation pathway showed a time-dependent induction of

211 ty of proteins known to be involved with the neddylation pathway.

212 Here we show that neddylation promotes SG assembly in response to arsenite

213 tants and monitored the cullin deneddylation/neddylation ratio during embryonic and early seedling de

214 stic studies demonstrated that inhibition of neddylation reduced both canonical and noncanonical nucl

215 Our results provide new insights into how neddylation regulates the conformation and activity of C

216 cullins by the ubiquitin-like protein NEDD8 (neddylation) regulates protein ubiquitination by promoti

217 nisms and biological consequence of atypical neddylation remain largely unexplored.

218 Thus, neddylation represents a novel molecular process in macr

219 emerging evidence demonstrates that cellular neddylation requires the action of Dcn1, which, in human

220 eddylase-1 (SENP8) as a key regulator of Cul neddylation response in vitro and in vivo.

221 Like ubiquitination, neddylation results from an enzymatic cascade involving

222 As a component of the E3 for neddylation, SCCRO/DCUN1D1 plays a key regulatory role i

223 on 1 domain containing 1/defective in cullin neddylation) serves as an accessory E3 in neddylation by

224 s inactivated by a mutation in its conserved neddylation site, and Nedd8 mutant neurons exhibit simil

225 entified that HBx K91 and K95 as the key HBx NEDDylation sites and observed that the NEDDylation-defi

226 We also identified the major NEDDylation sites on HBx.

227 evelopmentally regulated shift in the cullin neddylation status is absent in csn mutants.

228 r switch of CRLs activity by reverting their neddylation status, but its contribution to embryonic an

229 sponses to LPS or TNF-alpha by assessing Cul neddylation status, NF-kappaB and HIF-1alpha stabilizati

230 phosphorylation of VACM-1/Cul5 controls its neddylation status, phosphorylation by PKC, and ultimate

231 Here, we show that neddylation stimulates CRL activity by multiple mechanis

232 Thus, our results imply that neddylation stimulates ubiquitination by CRL conformatio

233 While many non-cullin neddylation substrates have been proposed over the years

234 Inhibition of neddylation suppressed the release of proinflammatory cy

235 The best understood neddylation targets are the cullins, scaffold subunits o

236 uitin-like posttranslational modification of neddylation, that conjugates Nedd8 (neural precursor cel

237 Recent work has revealed a central role for neddylation (the conjugation of a Nedd8-moiety to Cullin

238 reas NUB1L overexpression repressed atypical neddylation through promoting the degradation of NEDD8.

239 We also used siRNA to block neddylation to assess the role of this molecular process

240 DD8 and that the HDM2 E3 ligase promotes HBx NEDDylation to enhance HBx stability by inhibiting its u

241 On one hand, increased neddylation was associated with augmented caspase 3 acti

242 To identify genes that influence neddylation, we used a synthetic screen to identify gene

243 Loss of NUB1L exaggerated atypical neddylation, whereas NUB1L overexpression repressed atyp

244 Neddylation, which involves NEDD8 transfer from E2 to E3

245 s FBXO11 interacts with p53 and promotes its neddylation, which suppressed the p53 transactivity.

246 Numerous mechanisms specify cullin neddylation while preventing noncognate ubiquitin ligati