ライフサイエンスコーパス: SQSTM1

1 autophagy-associated proteins, including p62/SQSTM1.

2 y 5q in ccRCC is driven, at least partly, by SQSTM1.

3 LC3 and the autophagic adapter molecule p62/Sqstm1.

4 TSC: autophagy and the autophagy target p62/SQSTM1.

5 proteasomes and that autophagy degrades p62/SQSTM1.

6 fuse ubiquitinated proteins delivered by p62/SQSTM1.

7 ctron microscopy and the accumulation of p62/SQSTM1.

8 hich in some cases is caused by mutations in SQSTM1.

9 n event involving Nur77 interaction with p62/SQSTM1.

10 ction step by FACS to identify regulators of SQSTM1.

11 d accumulation of the autophagy receptor p62/SQSTM1.

12 recombinant, ubiquitin-associated domain of SQSTM1.

13 physically associates with OPTN, NDP52, and SQSTM1.

14 toring levels of the autophagy substrate p62/SQSTM1.

15 We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells

16 Phosphorylated p62/Sqstm1 accumulates in tumour regions positive for hepati

17 We also observed an increased p62/SQSTM1 accumulation in the cerebellum and reduced autoph

18 1 increased autophagosome number, LC3II, and SQSTM1 accumulation; Tat cotreatment diminished this eff

19 This is largely due to p62 (also called A170/SQSTM1) accumulation after autophagy inhibition.

20 2/SQSTM1 associated with proteasomes and p62/SQSTM1 aggregates contained inactive proteasomes, ubiqui

21 alysis of the cellular proteins LC3B and p62/SQSTM1, along with electron microscopy analysis, which d

22 Surprisingly, immunoreactive SQSTM1 also accumulated in the olfactory bulb of the bra

23 S leads to the localization of PARP12 to p62/SQSTM1 (an adaptor protein involved in innate signaling

24 LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded

25 or alpha (TNFalpha), CCL2, CXCL10, IL6R, and SQSTM1, an adaptor protein involved in nuclear factor ka

26 omycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-

27 Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NF-E2-related

28 anscription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induc

29 acroautophagy machinery as key regulators of SQSTM1 and identified several novel modulators including

30 uscin was now observed in motor neurons, and SQSTM1 and LC3 levels approached those of WT SOD1YFP mic

31 f the autophagy-associated proteins LC3, p62/SQSTM1 and nbr1.

32 ophagic activity, and excessively accumulate SQSTM1 and ubiquitin-bound proteins.

33 f autophagy-targeting antibodies specific to SQSTM1 and/or GABARAP.

34 A subset of cDNAs, encoding sequestosome 1 (SQSTM1) and dipeptidylpeptidase 3 (DPP3), activated the

35 iation of autophagosomal p62/sequestosome 1 (SQSTM1) and processed microtubule-associated protein 1 l

36 ns affecting the ubiquitin-binding domain of SQSTM1 are a common cause of familial and sporadic Paget

37 Optineurin and p62/SQSTM1 are independently recruited to separate domains o

38 so identified mutations in the gene encoding SQSTM1 as a common cause of familial and sporadic PDB.

39 direct and indirect mechanisms, pinpointing SQSTM1 as a key mediator of JunB suppression of NF-kappa

40 tin- and LC3-binding domains of OPTN and p62/SQSTM1 as well as the SKICH domains of NDP52 and TAX1BP1

41 With epoxomicin, soluble p62/SQSTM1 associated with proteasomes and p62/SQSTM1 aggreg

42 Our findings expand the SQSTM1-associated phenotypic spectrum and lend further s

43 We also provide strong evidence that p62/SQSTM1 associates with proteasomes and that autophagy de

44 Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate path

45 B activity and/or molecular targeting of p62/SQSTM1, Atg7, or cathepsin B result in partial reversal

46 There was increased expression of sqstm1, autophagy-related gene 5 (atg5) and light chain

47 hanism, the proteins WTX (AMER1), PALB2, and SQSTM1 bind KEAP1 to activate NRF2.

48 We found that the SQSTM1, but not GABARAP or LC3, associated with sperm mi

49 nalyses showed that JunB directly suppressed SQSTM1 by binding to a consensus AP-1 cis element locate

50 We show that ufmylation regulates SQSTM1 by eliciting a cell type-specific ER stress respo

51 SQSTM1 can bind to LC3 on autophagosomes and ubiquitinat

52 Three additional novel methylation loci-SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg136

53 We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) follow

54 ed soft agar growth, while downregulation of SQSTM1 decreased resistance to redox stress, impaired ce

55 of ubiquitinated protein aggregates and p62/SQSTM1, deficient LC3 conversion, and increased number o

56 as accumulation of autophagic vacuoles, p62(SQSTM1) degradation and conversion of Microtubule-associ

57 with a 2',5'-oligoadenylate resulted in p62(SQSTM1) degradation, LC3BI/LC3BII conversion, and appear

58 ircuit is reversed by ubiquitination and p62/SQSTM1-dependent autophagic degradation of CIP2A and sub

59 mammals thus relies on a combined action of SQSTM1-dependent autophagy and VCP-mediated dislocation

60 in, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that

61 BCR-ABL for autophagic degradation via a p62/SQSTM1-dependent mechanism that is critical for the anti

62 agosome formation and directly represses p62/SQSTM1 (encoding the autophagy adaptor p62) via TCF4.

63 with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate it

64 enzyme-inhibitory protein (vFLIP) increased SQSTM1 expression and activated Nrf2.

65 l of autophagy measured by inhibition of p62/SQSTM1 expression and cleavage of LC3.

66 pe-specific ER stress response which induces SQSTM1 expression and results in its accumulation in the

67 In GSCs, DRAM1 and SQSTM1 expression correlated with activation of MAPK and

68 or the ubiquitin proteasome pathway (PSMD7, SQSTM1, FLJ10111).

69 binding p62 scaffold protein (encoded by the SQSTM1 gene) regulates a diverse range of signalling pat

70 Amplification of the p62/Sqstm1 gene, and aberrant accumulation and phosphorylati

71 Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget diseas

72 Heterozygous variants in SQSTM1 have been associated with Paget disease of the bo

73 rant accumulation and phosphorylation of p62/Sqstm1, have been implicated in tumour development.

74 Overexpression of SQSTM1 in ccRCC lines promoted resistance to redox stres

75 mporal dementia (FTD), suggesting a role for SQSTM1 in FTD.

76 erent biallelic loss-of-function variants in SQSTM1 in nine affected individuals from four families w

77 pression of the autophagy cargo receptor p62/SQSTM1 in PI3K-H1047R cells is sufficient to enhance cel

78 with autophagic proteins such as MAP1LC3 and SQSTM1 in sIBM and other RV myopathies.

79 accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras(G12D) acinar cells is associated

80 Overall, the function of p62/SQSTM1 in the proteasomal pathway and autophagy requires

81 role of the adaptor p62 (encoded by the gene Sqstm1) in signaling functions central to tumor initiati

82 ht chain beta II (LC3II), and sequestosome 1(SQSTM1), in a membrane-enriched fraction, suggesting Tat

83 K pathway or by disruption of the VANGL2-p62/SQSTM1 interaction.

84 ctive autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in o

85 p62/Sqstm1 is a multifunctional protein involved in cell sur

86 SQSTM1 is an adaptor protein that integrates multiple ce

87 Here we demonstrate that p62/SQSTM1 is required for TLR4-mediated autophagy, which we

88 p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autopha

89 The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the meta

90 gh caspase-8 self-association depends on p62/SQSTM1, its self-processing requires the autophagosomal

91 le in an evolutionarily conserved VANGL2-p62/SQSTM1-JNK pathway.

92 LC3 with LDs was significantly inhibited by SQSTM1 knockdown, which also reduced ethanol-induced lip

93 ost autophagic markers (Beclin-1, ATG10, p62/SQSTM1, LC3) and of the HSPB8-mediated PQC response.

94 SQSTM1 levels were elevated in LTC, a consequence of pro

95 (OPTN), NDP52 (CALCOCO2), TAX1BP1, and p62 (SQSTM1) linking ubiquitinated cargo to autophagic membra

96 oprotein via a novel mechanism involving p62/SQSTM1-mediated localization of the oncoprotein to the a

97 in-like autophagy receptors [sequestosome 1 (SQSTM1), microtubule-associated protein 1 light chain 3

98 SPR is superior to RNAi in identifying known SQSTM1 modulators.

99 ouse sqstm1 (P394L), equivalent to the P392L SQSTM1 mutation in humans, develop a bone disorder with

100 A SQSTM1 mutation was first identified in a multiplex fami

101 in 750 individuals with PDB (cases) without SQSTM1 mutations and 1,002 controls and identified three

102 These studies demonstrate that SQSTM1 mutations can cause a PDB-like skeletal disorder

103 Patients with SQSTM1 mutations have severe Paget's disease of bone and

104 Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; descri

105 Recently, SQSTM1 mutations were confirmed in ALS, and mutations we

106 To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of

107 SQSTM1-Nup214, although mostly cytoplasmic, also forms n

108 Mutations of SQSTM1 occur in about10% of patients with Paget's diseas

109 Olfactory bulb SQSTM1 often congregated in activated microglial cells t

110 quitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol.

111 ution patterns of Atg5, Atg16, Atg9, and p62/SQSTM1 on the LC3-positive compartment provided new clue

112 amplification leads to overexpression of the SQSTM1 oncogene in ccRCC lines and tumors.

113 This suggests the possibility that SQSTM1 or damaged proteins may be transported from the n

114 r resulting from accumulated sequestosome 1 (SQSTM1 or p62) in Atg7(-)/(-) macrophages.

115 ing other autophagy genes, such as ATG5, p62/SQSTM1, or inhibiting autophagy pharmacologically by chl

116 Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAt

117 y, including an accumulation of striatal p62/SQSTM1 over time.

118 Similar to JunB loss of function, SQSTM1-overexpression induced TNFalpha, CCL2, and CXCL10

119 ne-leucine amino acid change at codon 392 of SQSTM1 (P392L) in French-Canadian patients with PDB.

120 ne to leucine mutation at codon 394 of mouse sqstm1 (P394L), equivalent to the P392L SQSTM1 mutation

121 e tumor cells preferentially accumulated p62/SQSTM1 (p62), endoplasmic reticulum (ER) chaperones, dam

122 Sequestosome 1 (SQSTM1)/p62 is an interacting partner of the atypical pr

123 SLiPs) into autophagosomes via sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs

124 is mediated by the ubiquitin-binding protein SQSTM1/p62 and the autophagy-related protein LC3, silenc

125 teraction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light

126 edox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K

127 k9/cyclin T1 transcriptionally downregulated SQSTM1/p62 but did not affect autophagic flux.

128 n autophagy and apoptosis, wherein targeting SQSTM1/p62 converts cytoprotective autophagy to an ineff

129 Mutations in the SQSTM1/p62 gene have been identified in up to 30% of Pag

130 The ubiquitin binding adaptor protein SQSTM1/p62 is required for the delivery of several ubiqu

131 Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner

132 In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading

133 nce of ubiquitinated aggregates during which SQSTM1/p62 plays a major role as a cargo adapter, we als

134 We confirmed absence of the SQSTM1/p62 protein in affected individuals' fibroblasts

135 Two markers of autophagy, sequestosome 1 (SQSTM1/p62) and microtubule-associated protein 1 light c

136 nctional scaffolding protein sequestosome-1 (SQSTM1/p62) confirmed autophagy.

137 The gene encoding sequestosome 1 (SQSTM1/p62) maps to within the PDB3 critical region, and

138 ion as evidenced by the accumulation of LC3, SQSTM1/p62, and ubiquitinated substrates in an expanded

139 expression of the autophagy adaptor protein, SQSTM1/p62, is associated with poor response to cetuxima

140 short hairpin RNA (shRNA) directly targeting SQSTM1/p62, resulted in cargo loading failure and ineffi

141 estigated the role of a key adaptor molecule SQSTM1/p62.

142 ns, and the multi-functional adapter protein SQSTM1/p62.

143 nt on the autophagic protein sequestosome-1 (SQSTM1; p62).

144 bition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion pr

145 drial-protein aging, and accumulation of p62/SQSTM1-positive mitochondria.

146 tanuclear accumulation of ubiquitin- and p62/SQSTM1-positive protein aggregates, and apoptotic cell d

147 6-basepair double-stranded DNA region of the SQSTM1 promoter to the Texas Instruments Spreeta, a surf

148 idence regarding the accumulation of the p62/SQSTM1 protein and ubiquitin-aggregated structures in th

149 We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and sho

150 Autophagic adapters including p62/SQSTM1 recognize polyubiquitinated targets such as toxic

151 ith the autophagy machinery, mediated by p62/SQSTM1 recruitment of RIPK1.

152 and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach

153 SQSTM1 (sequestosome 1; also known as p62) encodes a mul

154 ted two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal

155 ophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been impli

156 n this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1

157 Moreover, the SQSTM1 signal was colocalized with that of perilipin1, a

158 omotes the association of the protein to p62/SQSTM1, suggesting that the RNA-binding domain is respon

159 n in cortical neurons markedly increased p62/SQSTM1, supporting its degradation mainly by autophagy a

160 netic down-regulation of p62/sequestosome 1 (SQSTM1), the autophagy substrate that accumulates in TSC

161 these results demonstrate that KSHV induces SQSTM1 to constitutively activate Nrf2, which is involve

162 s OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus acce

163 t KSHV hijacks the host's autophagic protein SQSTM1 to induce Nrf2 activation, thereby manipulating t

164 Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuR

165 cis element located around 2 kb upstream of SQSTM1-transcription start site.

166 Association to p62/SQSTM1 was found to correlate with increased NF-kappaB s

167 In these cells, elevation of p62/SQSTM1 was greater upon proteasome inhibition than with

168 SQSTM1 was phosphorylated on serine-351 and -403, while

169 ry autophagy-targeting molecule p62 (A170 or SQSTM1) was required for mycobactericidal activity.

170 Like WTX, PALB2, and SQSTM1, we found that the dipeptidyl peptidase 3 (DPP3)

171 Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported

172 e most important of these is Sequestosome 1 (SQSTM1), which is a scaffold protein in the nuclear fact

173 nt on the autophagic protein sequestosome-1 (SQSTM1), which was involved in the degradation of the Nr

174 p62/SQSTM1, which accumulates in autophagy-defective cells,

175 autophagosomes were directed to the LDs via SQSTM1, which bound to ubiquitinated proteins, possibly

176 ded the autophagy-associated genes DRAM1 and SQSTM1, which encode a key regulator of selective autoph

177 in of 200 kDa) and the signaling adaptor p62/SQSTM1 within established murine tumors, which reveals a

178 enotype, active RHOA is sequestered via p62 (SQSTM1) within autolysosomes and fails to localize to th