ライフサイエンスコーパス: USP7

1 HSV-1), binds ubiquitin-specific protease 7 (USP7).

2 and cellular ubiquitin-specific protease 7 (USP7).

3 is for enhanced affinity and specificity for USP7.

4 e oligo-ubiquitinated and deubiquitinated by USP7.

5 UbE2E1 as well as the catalytic activity of USP7.

6 ting its interaction with the deubiquitinase USP7.

7 itin-conjugating enzyme that is regulated by USP7.

8 cribed by Kategaya as specific inhibitors of USP7.

9 hysically associates with the deubiquitinase USP7.

10 GNE-6640 and GNE-6776 non-covalently target USP7 12 A distant from the catalytic cysteine.

11 of a single amino acid to abolish binding to USP7 accelerated the accumulation of viral mRNAs and pro

12 summary, engineering compounds that inhibit USP7 activity by attenuating ubiquitin binding suggests

13 Loss of USP7 activity results in increased ubiquitination of NF-

14 Mechanistically, USP7 acts as a molecular rheostat to precisely fine-tune

15 ve identified ubiquitin-specific protease 7 (USP7; also known as HAUSP) as a regulator of N-Myc funct

16 g PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stab

17 gions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigo

18 1 at S380 accelerates complex formation with USP7 and CENPF to regulate their stability, thus having

19 ssays to probe the interaction between the C-USP7 and HSV-1 immediate-early protein ICP0 (infected ce

20 the "palm" region of the catalytic domain of USP7 and inhibit its catalytic activity.

21 overexpression decreases the association of USP7 and p53 and attenuates USP7-mediated p53 deubiquiti

22 Moreover, these data support the pursuit of USP7 and PHF8 as potential targets for breast cancer int

23 g cyclin A2 and that the interaction between USP7 and PHF8 is augmented during DNA damage.

24 xtended the UbE2E1 regulation of uH2AK119 to USP7 and showed that USP7 is also a key regulator for mo

25 o interacted with itself, whereas the TDs of USP7 and SPOP did not self-associate.

26 However, the close proximity of USP7 and telomerase binding sites on TPP1 suggest possib

27 ary to develop inhibitors targeting the DUBs USP7 and USP10, which are involved in regulating levels

28 Mechanistically, USP7 and USP11 regulate the ubiquitination status of the

29 eport that two ubiquitin-specific proteases, USP7 and USP11, co-purify with human PRC1-type complexes

30 Rather, OTUD4 is a scaffold for USP7 and USP9X, two deubiquitinases that act directly on

31 ated ubiquitin-specific protease; also named USP7) and blocked the access of p53 to the same region o

32 itin-specific protease (HAUSP, also known as USP7), and that the integrity of this molecular framewor

33 R) signaling, the TRAF domains (TDs) of MUL, USP7, and SPOP are located near the NH(2) termini or cen

34 aining TDs homologous to those found in MUL, USP7, and SPOP throughout eukaryotes, including yeast, p

35 ICP0, that ICP0 mediated the degradation of USP7, and that amino acid substitutions in ICP0 that abo

36 MUL and USP7 are capable of binding in vitro via their TDs to al

37 re, we identify the de-ubiquitylating enzyme USP7 as a critical regulator of Rad18 protein levels.

38 Taken together, these observations identify USP7 as a novel component of the cellular DDR involved i

39 Here we identify USP7 as a novel interacting protein of the oligonucleoti

40 Together, these results identify USP7 as a promising therapeutic target for the treatment

41 eubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-kappaB transcriptional activi

42 enzyme (DUB), ubiquitin-specific protease 7 (USP7), as a novel regulator of Poleta stability.

43 We demonstrate that USP7 associates with Rad18 directly via a consensus USP7

44 , KDM6A, SMARCA4, ASXL2, CREBBP, EZH2, MLL2, USP7, ASXL1, NSD2, SETD2, SMC1A and ZMYM3.

45 We show that USP7 attenuates UbE2E1-mediated ubiquitination, an effec

46 work of proteins, including the CCT complex, USP7, Aurora kinase, Nedd4, and Trim24, that bind mutant

47 mal and distal isotopic labels and measuring USP7 binding by nuclear magnetic resonance.

48 in the cell, consistent with their lack of a USP7 binding domain.

49 UbE2E1 in vitro and in vivo through the ASTS USP7 binding motif within its N-terminal extension in an

50 sion in an identical manner with other known USP7 binding proteins.

51 including ICP0 mutants that are defective in USP7 binding.

52 n that was abolished if either the ORF33- or USP7-binding domain in ORF45 was deleted.

53 erminal 19 amino acids (aa) of ORF45 and the USP7-binding domain to the reported consensus motif in t

54 sociates with Rad18 directly via a consensus USP7-binding motif and can disassemble Rad18-dependent p

55 its C-terminal UBL1-2 domains and mapped the USP7-binding site for ICP0.

56 USP7 binds directly to the supervillin N terminus and ca

57 served colocalization of ORF45 with ORF33 or USP7 both under transfected conditions and in KSHV-infec

58 Overexpression of wild-type USP7 but not its catalytically-defective mutants deubiqu

59 Overexpression of wild-type USP7, but not its catalytically inactive or interaction-

60 trate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulat

61 ting the therapeutic potential of inhibiting USP7 by this approach.

62 Although structures of the USP7 C terminus bound to its substrates could provide vi

63 The USP7 C-terminal region (C-USP7) contains five ubiquitin-

64 The USP7 C-terminal region (C-USP7) contains five ubiquitin-like domains (UBL1-5) that

65 ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC de

66 Moreover, USP7 deficiency severely impairs the repair of cyclobuta

67 olved in UV light-induced XPC degradation in USP7-deficient cells.

68 USP7-depleted cells also fail to elongate nascent daught

69 lusion of these studies is that depletion of USP7 destabilized ICP0, that ICP0 mediated the degradati

70 Loss of USP7 destabilizes Rad18 and compromises UV-induced PCNA

71 USP7 deubiquitinase activity is required for the stabili

72 attenuate ubiquitin binding and thus inhibit USP7 deubiquitinase activity.

73 Ubiquitin-specific protease 7 (USP7) deubiquitinates p53 and Hdm2 and regulates their s

74 Here, we show that the USP7 deubiquitinating enzyme is an integral component of

75 USP7 deubiquitination of NF-kappaB leads to increased tr

76 ort that the Ser18-containing isoform of the USP7 deubiquitylation enzyme (USP7S) controls Mule stabi

77 We have also found that USP7 directly binds ICP0 via its C-terminal UBL1-2 domai

78 tly focused on the mechanisms underlying how USP7 directly controls p53 stability, we recently showed

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

80 Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugate

81 The USP7-encoding gene was also transcriptionally regulated

82 pigmentosum variant) cells, suggesting that USP7 facilitates UV-induced PCNA monoubiquitination by s

83 Furthermore, we find that Usp7 forms a complex with GMP-synthetase (GMPS) to promo

84 USP7 forms a complex with UbE2E1 in vitro and in vivo th

85 pendent relocalization of a portion of ORF33/USP7 from the nucleus to the cytoplasm.

86 causative gene in Mulibrey Nanism syndrome; USP7 (HAUSP), an ubiquitin protease; and SPOP, a POZ dom

87 y, we show that the mammalian counterpart of Usp7, HAUSP, positively regulates Hh signaling by modula

88 Knockdown of the p53 deubiquitinating enzyme USP7/HAUSP also reverses the supervillin phenotype, bloc

89 iquitinating enzymes USP5/isopeptidase T and USP7/HAUSP and the ubiquitin ligases ARF-BP1/HUWE1 and p

90 The deubiquitylation enzyme USP7/HAUSP plays a major role in regulating genome stabi

91 ed by a deubiquitination enzyme and identify Usp7/HUASP as a critical regulator of Hh signaling and p

92 We have shown that depletion of the USP7 in HFF-1 cells negatively affects the efficiency of

93 quitinating enzyme, and establish a role for USP7 in human neurodevelopmental disease.

94 o heterozygous loss-of-function mutations of USP7 in individuals with a neurodevelopmental disorder,

95 NA interference (RNAi)-mediated knockdown of USP7 in neuroblastoma cancer cell lines, or genetic abla

96 er, our findings reveal a modulatory role of USP7 in PCNA ubiquitination-mediated stress-tolerance pa

97 our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by p

98 ma cancer cell lines, or genetic ablation of Usp7 in the mouse brain, destabilizes N-Myc, which leads

99 he ubiquitin-specific processing protease 7 (USP7) in paediatric leukaemia, which result in decreased

100 eubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage

101 Knockout of USP7 increased the steady-state level of Poleta and slow

102 st this hypothesis, we studied the effect of USP7 inhibition in chronic lymphocytic leukemia (CLL) wh

103 Consequently, USP7 inhibition induces significant tumor-cell killing i

104 Moreover, USP7 inhibition sensitized p53-defective, chemotherapy-r

105 dy therefore supports clinical evaluation of USP7 inhibitor, alone or in combination, as a potential

106 at interest exists, therefore, in developing USP7 inhibitors for clinical evaluation.

107 Perspective focuses on the current status of USP7 inhibitors from various organizations active in dev

108 gn, we describe the development of selective USP7 inhibitors GNE-6640 and GNE-6776.

109 to lead to successful clinical outcomes for USP7 inhibitors in cancer treatment.

110 th a unique N-terminal extension, is a novel USP7-interacting protein.

111 Here we show that USP7 interacts with and deubiquitinates Tip60 both in vi

112 We also showed that USP7 interacts with vIRF1 in U2OS cells.

113 USP7 is a deubiquitinase implicated in destabilizing the

114 USP7 is a protein deubiquitinase with an essential role

115 gulation of uH2AK119 to USP7 and showed that USP7 is also a key regulator for monoubiquitination at H

116 te that the deubiquitination of NF-kappaB by USP7 is critical for target gene transcription.

117 Additionally, USP7 is critical in maintaining the steady state levels

118 A clue as to why USP7 is degraded emerged from the observation that, notw

119 of USP7 leads to reduction of ICP0 and that USP7 is degraded in an ICP0-dependent manner.

120 pitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes.

121 USP7 is involved in the cellular stress response by regu

122 In addition, human USP7 is targeted by several viruses of the Herpesviridae

123 We demonstrate that USP7 is upregulated in CLL cells, and its loss or inhibi

124 Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme found in all eukaryot

125 Human ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that prevents protein

126 Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppr

127 mportant role in controlling other proteins, USP7 itself has not been recognized as a target for regu

128 a centrosomes, which is similar phenotype to USP7-knockdown cells.

129 Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated

130 We show here that, indeed, depletion of USP7 leads to reduction of ICP0 and that USP7 is degrade

131 USP7 localized predominantly to the nucleus, in a TD-dep

132 In addition to this, USP7 may also play a role in chromatin remodelling by di

133 This suggests that targeting USP7 may have therapeutic potential even in tumors with

134 n increases the Tip60 stability by promoting USP7-mediated deubiquitination of Tip60.

135 e association of USP7 and p53 and attenuates USP7-mediated p53 deubiquitination.

136 Here, we provide new evidence that USP7 modulated chromatin remodelling is important for ba

137 trols p53 stability, we recently showed that USP7 modulates the stability of the DNA damage responsiv

138 Analysis of various MUL and USP7 mutants by transient transfection assays indicated

139 ssays demonstrated that vIRF1 interacts with USP7-NTD via its EGPS motif.

140 cated that the vIRF1 peptide interacted with USP7-NTD with a Kd of 2.0 mum.

141 ed chemical perturbations after titration of USP7-NTD with vIRF1 (44)SPGEGPSGTG(53) peptide.

142 nteracts with the N-terminal domain of USP7 (USP7-NTD).

143 e of binding as that of the EBNA1 peptide to USP7-NTD.

144 The crystal structure of the USP7-NTD.vIRF1 peptide complex revealed an identical mod

145 However, overexpression of USP7 or substitution in ICP0 of a single amino acid to a

146 We were able to identify UbVs that bound USP7 or USP10 with high affinity and inhibited deubiquit

147 Ablation of either USP7 or USP11 in primary human fibroblasts results in de

148 Moreover, we show that loss of OTUD4, USP7, or USP9X in tumor cells makes them significantly m

149 nus, that is not mimicked by USP2A, USP4, or USP7, other members of the deubiquitination catalytic fa

150 Also, USP7 physically binds Poleta in vitro and in vivo.

151 We show that USP7 physically interacts with XPC in vitro and in vivo.

152 ubiquitin Lys48 side chain, suggesting that USP7 preferentially interacts with and cleaves ubiquitin

153 Furthermore, ectopic expression of USP7 promoted the UV-induced proliferating cell nuclear

154 Moreover, USP7-promoted PHF8 stabilization conferred cellular resi

155 We showed that USP7 promotes breast carcinogenesis by stabilizing PHF8

156 Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8

157 oup, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrat

158 Here we report that USP7 regulates nucleotide excision repair (NER) via deub

159 USP7 regulates Poleta stability through both indirect an

160 Here, we provide evidence that USP7 regulates the activity of Polycomb repressive compl

161 USP7 regulates the posttranslational status of RING1B an

162 for example, ubiquitin-specific protease-7 (USP7) regulates stability of the p53 tumour suppressor a

163 Here, we report that USP7 regulation plays a central role in DNA damage signa

164 2A Lys-119 as both knockdown and deletion of USP7 results in decreased levels of uH2AK119.

165 inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 lig

166 stitutions in ICP0 that abolished binding to USP7 significantly impaired the ability of HSV-1 to repl

167 We show that transient USP7 siRNA knockdown did not change the levels or activi

168 d understanding the molecular mechanism of C-USP7 specificity toward its substrates and may provide t

169 Thus, not only does USP7 stabilize PRC1 components, its catalytic activity i

170 ed ubiquitin-specific protease (Hausp, a.k.a Usp7), stabilizing Cry1 and shifting circadian clock tim

171 provide vital information for understanding USP7 substrate specificity, no such data has been availa

172 rget engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53,

173 domains (UBL1-5) that interact with several USP7 substrates.

174 Consistent with USP7 target engagement in cells, FT671 destabilizes USP7

175 We identify amino acids in TPP1 and USP7 that are critical for their interaction and multipl

176 Ubiquitin specific protease 7 (USP7), the most widely studied among the nearly 100 deub

177 sis included the ubiquitin-specific protease USP7, the transcriptional repressor TRIM27, DNA repair p

178 the binding of a ubiquitin-specific protease Usp7 to Ci, which positively regulates Hh signaling acti

179 Our study mechanistically links USP7 to epigenetic regulation and DNA repair.

180 deregulation of the deubiquitinating enzyme USP7 to inhibit p53-mediated antiviral responses.

181 factor Elongin BC and the H2B deubiquitinase USP7 to modulate transcriptional processes in mESCs simi

182 In this work we have demonstrated that the USP7 ubiquitin-like domains can be studied in isolation

183 al ORF33 and the 130-kDa protein is cellular USP7 (ubiquitin-specific protease 7).

184 In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, reg

185 that interacts with the N-terminal domain of USP7 (USP7-NTD).

186 ls, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by th

187 level of the claspin deubiquitinating enzyme USP7 was detected.

188 USP7 was overexpressed in breast carcinomas, and the lev

189 tic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases.

190 1 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to c

191 that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and wit

192 dulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1

193 Inhibiting USP7 with the small-molecule inhibitor P22077 attenuates

194 tribution of the ubiquitin-specific protease USP7 within the cell, consistent with their lack of a US