ライフサイエンスコーパス: DUB

1 DUB inhibitors, especially the inhibitors of proteasomal

2 DUB profiling identified 28 DUBs that cleave DIX-ubiquit

3 DUBs used in UbiCRest can be obtained commercially; howe

4 DUB profiling identified 28 DUBs that cleave DIX-ubiquitin conjugates, half of which

5 Despite the ~90 DUBs in human cells, including two others in addition to

6 onstrate that in addition to its action as a DUB inhibitor, PR-619 is a potent DNA topoisomerase II (

7 To explore how the BRCA1-A DUB activity contributes to its function at DNA double s

8 We engineered a DUB mutation (Asp1772 to Ala) into a murine coronavirus

9 la pneumophila SidE effector family harbor a DUB module important for ubiquitin dynamics on the bacte

10 oronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, an

11 r, some CI-inducing Wolbachia strains lack a DUB-encoding cid operon; it was therefore proposed that

12 TU domain-containing protein 7B (OTUD7B)), a DUB that controls key cellular functions and signaling p

13 (PGP9.5) and Parkinson disease 5 (PARK5), a DUB active in neurons that constitutes 1 to 2% of the to

14 and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly ex

15 ed histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allowi

16 Our data reveal a DUB-dependent mechanism of ANKRD protein homeostasis, th

17 ves a putative nuclease (CinB) rather than a DUB.

18 Through a DUB RNAi screen, we found OTUD5 as a specific stabilizer

19 ubiquitin-binding led to a much more active DUB.

20 believe the field of drug discovery against DUBs is still in its infancy, but advances in assay deve

21 screen in breast cancer cells targeting all DUBs identified USP11 as a regulator of ERalpha transcri

22 es the viral replicase polyprotein, and also DUB activity (deconjugating ubiquitin/ubiquitin-like mol

23 at inhibits its interaction with ASXL1/2 and DUB activity and deregulates cell proliferation.

24 ric inhibitors of the ubiquitin E1-E2-E3 and DUB enzymatic cascade developed over the past decade wit

25 The HAT and DUB modules are in close proximity, and the DUB module m

26 f a nucleosome to SAGA displaces the HAT and DUB modules from the core-module surface, allowing the D

27 nation and deubiquitination by E3 ligase and DUB machinery positioned at the gate.

28 pregulation of E3 Ubiquitin ligase HUWE1 and DUBs like USP9X and UBP7 in both tumor and metastatic le

29 findings demonstrate that USP7 and USP10 are DUBs that regulate NHE3 ubiquitination and expression, a

30 Successful capture of the TRIM-25-associated DUB, ubiquitin specific protease 15, demonstrated the ve

31 via targeting the 19S proteasome-associated DUBs (UCHL5 and USP14), without effecting on the 20S pro

32 ione inhibits both 19S proteasome-associated DUBs and 20S proteasome activity with a mechanism distin

33 ct the contribution of proteasome-associated DUBs and the complexity of the degradation process.

34 Unlike the ATXN7L3 DUB complex, a USP22-ATXN7L3B-ENY2 complex cannot deubiq

35 Bacterial DUBs have been discovered, but little is known about the

36 XL2 cancer-associated mutations disrupt BAP1 DUB activity.

37 is study investigates the importance of BAP1 DUB activity and the interactions with FoxK2 and HCF-1 i

38 target genes, and this effect requires BAP1 DUB activity but not interaction with HCF-1.

39 ve fluorescent small-molecule activity-based DUB probe that is active in live cells and an in vivo an

40 of the previously published MALDI-TOF-based DUB assay method.

41 Inactivating BRCC36 DUB attenuated BRCA1-A functions at DSBs and led to unre

42 ur findings uncover a pivotal role of BRCC36 DUB in limiting DSB processing and repair and illustrate

43 Our work explains modularity in the BRCC36 DUB family, with different adaptor subunits conferring d

44 a new regulatory mechanism underlying BRCC36 DUB activity, subcellular localization, and biological f

45 transcription factors, induction of IDOL by DUB inhibition is LXR-independent and occurs in Lxralpha

46 In addition, cleavage of the K48 linkage by DUB is faster if this linkage is at the distal end.

47 the in vitro cleavage of ubiquitin chains by DUBs.

48 alytic activity of and target recruitment by DUBs need to be tightly controlled.

49 aged cell-permeable ubiquitin probe captured DUBs specifically in respective G1/S and G2/M phases in

50 ariant of ubiquitin (HA-Ub-VME), we captured DUBs that are differentially recruited to the cytosol on

51 distinct ways, either by using its catalytic DUB activity or in a noncatalytic manner by inhibiting t

52 used pharmacological inhibition of cellular DUB activity.

53 ion at which PR-619 exhibits robust cellular DUB inhibitor activity (5-20 muM) is similar to the lowe

54 inkage ubiquitination due to lack of Cezanne DUB activity compromises the recruitment of Rap80/BRCA1-

55 seudo DUB allosterically activates a cognate DUB partner and implicates super dimerization as a new r

56 Contrary to the most common DUB screening technologies currently available, the MALD

57 identical substrates than their constituent DUBs by roughly 2 orders of magnitude.

58 These results establish M40-containing DUB complexes as novel HSC regulators of HSC expansion,

59 rved and widely used mechanism that controls DUB availability and function.

60 cate that abolishing/reducing the deISGylase/DUB activity of Lpro causes viral attenuation independen

61 ase activity, Lpro acts as a deubiquitinase (DUB) and deISGylase.

62 ed in cancer, functions as a deubiquitinase (DUB) for histone H2A.

63 s, and identified USP20 as a deubiquitinase (DUB) that regulates SNAI2 ubiquitination and stability.

64 acetyltransferase (HAT) and deubiquitinase (DUB) activities.

65 opmental-disorder-associated deubiquitinase (DUB).

66 talytic domains of different deubiquitinase (DUB) enzymes, with different specificities for polyubiqu

67 nesis, while loss of the H2B deubiquitinase (DUB) activity does not.

68 (UbV) inhibitors of a human deubiquitinase (DUB), ubiquitin-specific protease 2 (USP2).

69 Inhibiting deubiquitinase (DUB) function is a promising strategy for the treatment

70 gly, an MHV68 mutant lacking deubiquitinase (DUB) activity, embedded within the large tegument protei

71 blation of the mitochondrial deubiquitinase (DUB) USP30 triggers accumulation of Ub-substrates that a

72 requiring the nucleoplasmic deubiquitinase (DUB) USP1 and the nucleolar DUB USP36.

73 Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy

74 derivatives block proteasome deubiquitinase (DUB) activity and have been developed and tested in the

75 nd that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly

76 The deubiquitinase (DUB) and tumor suppressor BAP1 catalyzes ubiquitin remov

77 t in ATXN7, a subunit of the deubiquitinase (DUB) module (DUBm) in the SAGA complex.

78 leagues demonstrate that the deubiquitinase (DUB) OTUB1 is frequently overexpressed in human cancers,

79 The deubiquitinase (DUB) Ubp10 is thought to promote heterochromatic silenci

80 erent viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonucle

81 we investigated the role of deubiquitinases (DUB) in regulating ERalpha in breast cancer.

82 Deubiquitinases (DUBs) are vital for the regulation of ubiquitin signals,

83 Deubiquitinases (DUBs) remove ubiquitin conjugates from diverse substrate

84 Deubiquitinases (DUBs) reverse ubiquitin signals with equally high sophis

85 domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in

86 a class of enzymes known as deubiquitinases (DUBs).

87 f two proteasome-associated deubiquitinases (DUBs), Rpn11 and Ubp6, and explored their impact on over

88 ing through its reversal by deubiquitinases (DUBs).

89 uitin chains is mediated by deubiquitinases (DUBs).

90 omponents, particularly key deubiquitinases (DUBs) of the ubiquitin-specific protease (USP) class.

91 rate, and susceptibility to deubiquitinases (DUBs) affect processing of different substrates by prote

92 n be antagonized by various deubiquitinases (DUBs) including the CYLD tumour suppressor that attenuat

93 , as are a variety of viral deubiquitinases (DUBs).

94 icase polyprotein and as a deubiquitinating (DUB) enzyme which removes ubiquitin (Ub) moieties from u

95 onjugating, E3 ligase, and deubiquitinating (DUB) enzymes offers an ideal platform for modulating act

96 of an Lnk-associated Lys63 deubiquitinating (DUB) complex, attenuates HSC expansion.

97 in subcomplex known as the deubiquitinating (DUB) module.

98 hows that the SAGA histone deubiquitination (DUB) module lengthened period similarly to Nipped-A RNAi

99 AT) module and the histone deubiquitination (DUB) module.

100 y effector protein bearing a deubiquitylase (DUB) domain from the obligate intracellular bacterium Or

101 ction of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado-Joseph Disease (MJD), remains e

102 Triazole-based deubiquitylase (DUB)-resistant ubiquitin (Ub) probes have recently emerg

103 n but is endowed with K63-Ub deubiquitylase (DUB) activity.

104 en E3 ubiquitin ligases and deubiquitylases (DUBs).

105 s, and novel substrates for deubiquitylases (DUBs) and Ub ligases (E3s).

106 examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes protea

107 und that both forms of ATXN7 greatly enhance DUB activity but that ATXN7-92Q NT is largely insoluble

108 is a broad-spectrum deubiquitinating enzyme (DUB) inhibitor that has been employed in cell-based stud

109 tudy is to identify deubiquitinating enzyme (DUB) regulating the post-endosomal fate of human NHE3.

110 a Zn(2+)-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains a

111 idase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein s

112 binds and activates deubiquitinating enzyme (DUB) UCHL5/Uch37.

113 d activation of the deubiquitinating enzyme (DUB) USP8.

114 have identified the deubiquitinating enzyme (DUB), ubiquitin-specific protease 7 (USP7), as a novel r

115 udied; however, the deubiquitinating enzyme (DUB), which regulates TRAF2 stability, has not been iden

116 ow that a Wolbachia deubiquitylating enzyme (DUB) induces CI.

117 mains unclear which deubiquitylating enzyme (DUB) removes H2AK13,15ub.

118 Here we reveal the deubiquitylating enzyme (DUB) ubiquitin-specific protease 32 (USP32) as a powerfu

119 CidB, the latter a deubiquitylating enzyme (DUB), recapitulates CI in transgenic Drosophila melanoga

120 is catalyzed by a De-UBiquitylating enzyme (DUB).

121 itination, yet few deubiquitinating enzymes (DUB) have been implicated.

122 ffectively inhibit deubiquitinating enzymes (DUB), including the enzymes USP9x and UCH37, which are a

123 ins is mediated by deubiquitylating enzymes (DUB) such as OTUB1, which plays an important role in imm

124 eting of all human deubiquitinating enzymes (DUBs) and identify their essentiality for cell fitness.

125 Deubiquitinating enzymes (DUBs) are a growing target class across multiple disease

126 inating as well as deubiquitinating enzymes (DUBs) can regulate these processes by modifying the ubiq

127 Deubiquitinating enzymes (DUBs) have emerged as key players in the maintenance of

128 f linkage-specific deubiquitinating enzymes (DUBs) in parallel reactions, followed by gel-based analy

129 Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquiti

130 Deubiquitinating enzymes (DUBs) regulate various cellular processes ranging from p

131 Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrate

132 that regulate the deubiquitinating enzymes (DUBs) responsible for the removal of ubiquitin from targ

133 s regulated by the deubiquitinating enzymes (DUBs) Ubp2 and Ubp15.

134 ent complexes with deubiquitinating enzymes (DUBs) USP2 and USP7, highlighting the use of our new met

135 utionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall doma

136 tivity of cellular deubiquitinating enzymes (DUBs) with the much needed temporal control.

137 Deubiquitinating enzymes (DUBs), which reverse the process of ubiquitination, are

138 proteasome system, deubiquitylating enzymes (DUBs) not only help generate and maintain the supply of

139 Deubiquitylating enzymes (DUBs) play a vital role in the ubiquitin pathway by edit

140 Deubiquitylating enzymes (DUBs) remove ubiquitin (Ub) from various cellular protei

141 pproach to uncover deubiquitylating enzymes (DUBs) that participate during TCR signaling in primary m

142 ent on activity of deubiquitylating enzymes (DUBs).

143 Found in all eukaryotes, MINDY-family DUBs are highly selective at cleaving K48-linked polyUb,

144 lysosomal degradation of the LDLR following DUB inhibition.

145 roteins, ATXN7L3 and ENY2, are necessary for DUB activity toward histone H2Bub1 and other substrates.

146 heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHM

147 Our results uncover a novel function for DUBs in the endocytic pathway by which Ubp2 and Ubp15 po

148 rategy for rational design of inhibitors for DUBs and other UPS proteins.

149 e observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of

150 - and loss-of-function screens using a human DUB cDNA library of 65 genes and an siRNA library of 98

151 Of the hundreds of human DUBs, USP11 has emerged as an ideal therapeutic target,

152 iew, we discuss the recent findings on human DUBs that participate in genome maintenance, with a focu

153 requently double up as ubiquitin hydrolases (DUB), thus interfering with cellular processes critical

154 Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial

155 ell-permeable ubiquitin probe and identified DUBs captured by the probe using label-free quantitative

156 over 50 reported inhibitors and advances in DUB structural studies, assay formats, and chemical biol

157 a framework to tackle lingering questions in DUB biology.

158 e it into eggs, and a catalytically inactive DUB does not induce sterility.

159 The CI-inducing DUB, CidB, cleaves ubiquitin from substrates and is enco

160 a new mechanism of NHE3 inhibition involving DUBs.

161 nism between the silencing machinery and its DUB partner allows erasure of active PTMs and the de nov

162 subunit that confers the BRCA1-A complex its DUB activity.

163 in fold with no homology to any of the known DUBs.

164 The Ulp1-like DUB prefers ubiquitin substrates over ubiquitin-like pro

165 articularly coronaviruses, suggests that low DUB activities of viral PRO/DUBs may generally be fine-t

166 s of the OTU and JAB/MPN/Mov34 metalloenzyme DUB families and highlight that all USPs tested display

167 (STAM) (AMSH) is a conserved metalloprotease DUB in eukaryotes.

168 activity based probes and assays to monitor DUB activities in vitro and in cellular contexts.

169 enetic and functional studies have nominated DUBs as a promising class for drug discovery across dive

170 (motif interacting with Ub-containing novel DUB family).

171 tudy provides an important step toward novel DUB inhibitors that may reduce the resistance of some ca

172 deubiquitinase (DUB) USP1 and the nucleolar DUB USP36.

173 for a wide range of DUBs and advancement of DUB-targeting drugs to the clinic.

174 A new family of DUB-resistant Ub probes is reported based on isopeptide-

175 nable a conceptually intriguing interplay of DUB oligomerization and activity.

176 We further discuss the many mechanisms of DUB regulation with a focus on those that modulate catal

177 t interferon (IFN) response, but the role of DUB activity during virus infection was unknown.

178 e reported on the regulatory significance of DUB-E3 interactions and it is becoming clear that they p

179 an alternative strategy for the analysis of DUBs that are recalcitrant to phage display and other in

180 uitin conjugates to study various aspects of DUBs such as their specificities and structures.

181 in-specific proteases (USP) are one class of DUBs that have drawn special attention as cancer targets

182 ectively, our results reveal a new family of DUBs that may have specialized roles in regulating prote

183 e we report the discovery of a new family of DUBs, which we have named MINDY (motif interacting with

184 r understanding of the cellular functions of DUBs.

185 cal entities for the selective inhibition of DUBs based on these tools are also highlighted with sele

186 hat the isothiocyanate-induced inhibition of DUBs may also explain how isothiocyanates affect inflamm

187 Short term (2 h) inhibition of DUBs resulted in accumulation of high molecular weight u

188 orm for the development of UbV inhibitors of DUBs in vivo, providing an alternative strategy for the

189 and selective inhibitors for a wide range of DUBs and advancement of DUB-targeting drugs to the clini

190 Concurrent with the revelation of DUBs as potential therapeutic targets are publications o

191 Studying the role of DUBs in health and diseases has been a major goal for ma

192 ome maintenance, with a focus on the role of DUBs in the modulation of DNA repair and DNA damage sign

193 Consistent with the role of DUBs in transcriptional regulation, we identified a 70-b

194 The role of DUBs is poorly understood in neurodegenerative diseases.

195 e points to the important regulatory role of DUBs, the molecular basis of their regulation is still n

196 The roles of DUBs in regulation of NHE3 were studied by determining t

197 R proteins, we propose that stabilization of DUBs by their interacting WDR proteins may be a conserve

198 es (UCHs) belong to an enzymatic subclass of DUBs, and are represented by three members in Arabidopsi

199 ese advances in pharmacological targeting of DUBs establish the enzyme family as targetable and provi

200 The effects of ATXN7-poly(Q) on DUB activity are not known.

201 One DUB whose function has been proposed to include monoubiq

202 USP19, the only DUB containing a carboxyl-terminal transmembrane domain,

203 Deubiquitinating enzymes, or DUBs, comprise a family of proteases that regulate ubiqu

204 iverse roles of deubiquitinating enzymes, or DUBs, in determining the fate of specific proteins conti

205 hat have been used to identify E3 ligases or DUBs to facilitate the search for yet-to-be discovered u

206 Correspondingly, the ORF64 DUB active site mutant virus exhibited impaired ability

207 n melanoma 2 pathways, and lack of the ORF64 DUB was associated with impaired delivery of viral DNA t

208 ed here are specific to UCHL1 over all other DUBs detectable by competitive activity-based protein pr

209 L5 activity cannot be fully assumed by other DUBs.

210 targetable and provide a framework for other DUBs programs.

211 This interaction strongly stimulated OTUB1 DUB activity toward Lys-48-linked diubiquitin.

212 Previous in vitro studies implicated PLP2/DUB activity as a negative regulator of the host interfe

213 of the PLP2-ubiquitin complex and that PLP2/DUB activity plays a role as an interferon antagonist in

214 results of this study demonstrate that PLP2/DUB is an interferon antagonist and a virulence trait of

215 Although PR-DUB was previously shown to cooperate with PRC2, we obse

216 f the Polycomb repressive deubiquitinase (PR-DUB) complex, both of which act to remove monoubiquitin

217 alian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on

218 the Polycomb repressive deubiquitination (PR-DUB) complex.

219 Mutations in PR-DUB components are frequent in cancer.

220 an important functional role for ASXL3 in PR-DUB mediated deubiquitination.

221 However, mechanistic understanding of PR-DUB function in gene regulation is limited.

222 lectively, these results demonstrate that PR-DUB, by counteracting accumulation of H2AK119ub1, mainta

223 ed a strategy to selectively disable PL(pro) DUB activity, we were able to specifically examine the e

224 eported the crystal structures of such a PRO/DUB from Turnip yellow mosaic virus (TYMV) and of its co

225 We find that PRO/DUB recognizes ubiquitin in an unorthodox way: It intera

226 roducing a single-point mutation in TYMV PRO/DUB aimed at improving ubiquitin-binding led to a much m

227 we report the crystal structure of TYMV PRO/DUB in complex with ubiquitin.

228 Comparison with other PRO/DUBs from other viral families, particularly coronavirus

229 uggests that low DUB activities of viral PRO/DUBs may generally be fine-tuned features of interaction

230 Moreover, using this probe DUBs were profiled at different time points following th

231 n effective inhibitor of the 19S proteasomal DUBs and suggests a potentially new strategy for cancer

232 rs, especially the inhibitors of proteasomal DUBs are becoming a research hotspot in targeted cancer

233 VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed m

234 explored their impact on overall proteasome DUB activity.

235 ide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner and i

236 domain protein BRCC36 associates with pseudo DUB MPN(-) proteins KIAA0157 or Abraxas, which are essen

237 details for generating a toolkit of purified DUBs and for profiling their linkage preferences in vitr

238 probe showed good reactivity toward purified DUBs, including USP2, UCHL1, and UCHL3, upon photoirradi

239 residues results in a PLP2 that has reduced DUB activity but retains protease activity.

240 iquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein processing ac

241 ulated in yeast by CidB alone; this requires DUB activity but is rescued by coexpressed CidA.

242 at ATXN7L3B regulates H2Bub1 levels and SAGA DUB activity through competition for ENY2 binding.

243 he day to promote transcription through SAGA DUB and Tip60 HAT activity.

244 r the identification of potent and selective DUB modulators.

245 Several DUBs have been implicated in various diseases and are at

246 ystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals t

247 ew, we highlight recent successes in solving DUB-ligand co-structures and the development of rigorous

248 Thus, USP7 directly serves as a specific DUB for Poleta.

249 The development of specific DUB inhibitors, together with inhibitors of BoNT/A prote

250 there is an urgent need to identify specific DUBs associated with therapeutically relevant targets of

251 ) via targeting both 19S proteasome-specific DUBs and 20S proteolytic peptidases with a mechanism dis

252 strategy toward identifying target-specific DUBs.

253 cal data provide the rationale for targeting DUB enzyme Rpn11 upstream of 20S proteasome to enhance c

254 ptualize the many layers of specificity that DUBs encompass to control the ubiquitin code and discuss

255 s from the core-module surface, allowing the DUB module to bind one face of an ubiquitinated nucleoso

256 DUB modules are in close proximity, and the DUB module modestly stimulates HAT function.

257 sequencing) analysis revealed that both the DUB and HAT modules bind most SAGA target genes even tho

258 ecombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activate

259 earby nucleophilic cysteine residue from the DUB active site.

260 enocysteine-based strategies to generate the DUB probe dehydroalanine (Dha).

261 However, the DUB module regulates a subset of genes in early embryoge

262 These findings directly implicate the DUB function of PL(pro), and not its proteolytic activit

263 These results show that USP51 is the DUB for H2AK13,15ub and regulates DNA damage response.

264 The co-crystal structure of the DUB (OtDUB) domain with ubiquitin revealed three bound u

265 USP22 is the catalytic subunit of the DUB module, but two adaptor proteins, ATXN7L3 and ENY2,

266 ated the replication and pathogenesis of the DUB mutant virus (DUBmut) in cultured macrophages and in

267 enes in early embryogenesis, and loss of the DUB subunits causes defects in embryogenesis.

268 In this study, we report the DUB USP9X is an important regulator of the core kinases

269 ugh many of these targets do not require the DUB module for expression.

270 To separate the DUB activity from the protease activity, we employed a s

271 o the Tra1 module, whereas Sgf73 tethers the DUB module.

272 Furthermore, we found that the DUB module can bind to chromatin and regulate transcript

273 We find that the DUB module deubiquitinates H2B both in the context of th

274 Our results suggest that the DUB module has functions within SAGA and independent fun

275 a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine

276 o express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon

277 We have previously shown that the DUB ubiquitin-specific protease 46 (USP-46) removes ubiq

278 Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasi

279 library to develop inhibitors targeting the DUBs USP7 and USP10, which are involved in regulating le

280 These DUBs thus have the potential to promote Dvl polymerizati

281 1-3 are not yet known, we propose that these DUBs act on one or more factors that control period leng

282 tion should be exercised when employing this DUB inhibitor in cell-based studies.

283 or maintaining proper protein levels of this DUB.

284 milar to its human counterpart and that this DUB is necessary during fly development.

285 Our results suggest that in addition to DUB inhibition, these compounds induce nonspecific prote

286 biquitination in HSC signaling, and point to DUB-specific inhibitors as reagents to expand stem cell

287 sive element, which mediates the response to DUB inhibition.

288 this isopeptide replacement is resistant to DUBs and to shaving by proteasome.

289 hnologies currently available, the MALDI-TOF DUB assay combines the use of physiological substrates w

290 In a MALDI-TOF DUB assay, we quantitate the amount of mono-ubiquitin ge

291 Intriguingly, we found that the K63-Ub DUB activity, although dispensable for maintaining the i

292 cific proteases (USPs) are de-ubiquitinases (DUBs) that control protein ubiquitination cycle.

293 We find that Sir2/4 stimulates Ubp10 DUB activity on nucleosomes, likely through a combinatio

294 how that USP51, a previously uncharacterized DUB, deubiquitylates H2AK13,15ub and regulates DNA damag

295 , ultimately resulting in increases in USP48 DUB activity.

296 killed by small-molecule inhibitors of USP8 (DUBs-IN-3/compound 22c) and the NEDD8 E1 activating enzy

297 ensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorpti

298 ubiquitin code and discuss examples in which DUB specificity has been understood at the molecular lev

299 us infection in macrophages, consistent with DUB activity negatively regulating the IFN response.

300 ctively, and can be used in combination with DUBs to generate K29- and K33-linked chains for biochemi