ライフサイエンスコーパス: SCAP

1 SCAP (SREBP cleavage-activating protein) forms a complex

2 SCAP (SREBP cleavage-activating protein) is a sterol-reg

3 SCAP [sterol-regulatory element-binding protein (SREBP)

4 SCAP appears to be a central regulator of cholesterol me

5 SCAP budding was diminished in membranes from sterol-tre

6 SCAP has multiple membrane-spanning regions, five of whi

7 SCAP RNAi or 25-HC inhibited VEGF-induced pseudopodia ex

8 SCAP then recycles to the ER for additional rounds of SR

9 SCAP-deficient mice showed an 80% reduction in basal rat

10 SCAP-stimulated proteolysis releases active fragments of

11 determination of drug concentrations using a SCAP DBS system for online extraction and analysis of dr

12 molecular detail, but little is known about SCAP recycling.

13 mutation, which correspond to the activating SCAP L315F and D443N mutations, respectively, exhibit a

14 the complex between full-length SREBP-2 and SCAP as measured by co-immunoprecipitation.

15 r findings were observed for SCAP(D443N) and SCAP(Y298C), both of which cause a sterol-resistant phen

16 ted in the same manner as those of HMG-R and SCAP, providing strong evidence that this domain is func

17 terol-sensing domains, HMG CoA reductase and SCAP.

18 SREBPs and SCAP are joined together in ER membranes through interac

19 ons of SCAP do not occur, apparently because SCAP fails to leave the ER.

20 cholesterol, by retaining complexes between SCAP and SREBP in the ER.

21 ression, insig-1, but not insig-2, can block SCAP movement in the absence of exogenous sterols.

22 dedicated to SCAP, or whether sterols block SCAP incorporation into common coat protein (COP)II-coat

23 Sterols block SCAP incorporation into vesicles by blocking Sar1-depend

24 ere designed to reveal whether sterols block SCAP movement by inhibiting synthesis of special vesicle

25 lanation for the ability of sterols to block SCAP.SREBP movement from the ER and thereby to control l

26 Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven gliobla

27 s overexpression amplifies sterol sensing by SCAP/SREBP-2.

28 This change causes SCAP to bind to Insigs, which are endoplasmic reticulum

29 es were isolated from sterol-depleted cells, SCAP entered vesicles in a reaction requiring nucleoside

30 In sterol-depleted cells, SCAP escorts SREBPs from ER to Golgi for proteolytic pro

31 In sterol-depleted cells, SCAP escorts SREBPs from ER to Golgi, where SREBPs are c

32 In sterol-depleted cells, SCAP facilitates cleavage of SREBPs by Site-1 protease,

33 t regulator of SCAP in vivo, fails to change SCAP's conformation in vitro, suggesting that oxysterols

34 rol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER r

35 ion of PI3K/Akt in addition to the chaperone SCAP and protease S1P.

36 We defined SCAP as receipt of intensive therapy in the intensive ca

37 l interest for the application of delivering SCAP in their original niche, as compared with use of a

38 Depleting SCAP using short hairpin RNA (shRNA) showed that SREBP1

39 In the SRD-13A cells, the only detectable SCAP allele encodes a truncated nonfunctional protein.

40 vating protein (SCAP), because knocking down SCAP by RNA interference (RNAi) inhibited SREBP activati

41 atogenic potential of BMSCs v/s DMSCs (DPSC, SCAP & DFSC) along-with secretome characterization.

42 ay analysis revealed the interaction of DPSC/SCAP secretome proteins and these proteins were found to

43 is more potent than cholesterol in eliciting SCAP binding to Insigs, but 25-HC does not cause a detec

44 a putative 25-HC sensor protein that elicits SCAP-Insig binding.

45 transfected with expression vectors encoding SCAP.

46 Cells that express SCAP(Y298C) continued to process SREBPs in the presence

47 had virtually no effect in cells expressing SCAP(D443N) or SCAP(Y298C).

48 nd evaluate a health-services definition for SCAP.

49 transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs.

50 1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct tar

51 Similar findings were observed for SCAP(D443N) and SCAP(Y298C), both of which cause a stero

52 REBP cleavage, suggesting a central role for SCAP as a sterol sensor in liver.

53 cs of ER exit in living cells expressing GFP-SCAP.

54 with a fibrin hydrogel with or without human SCAP.

55 ults demonstrate a novel role for LH/cAMP in SCAP/SREBP activation and subsequent regulation of stero

56 -2 also enhance the conformational change in SCAP that occurs upon addition of certain cationic amphi

57 s in vitro causes a conformational change in SCAP, detected by the unmasking of closely spaced trypsi

58 itro to produce the conformational change in SCAP.

59 cause a detectable conformational change in SCAP.

60 ing to hydrophobic sterol-sensing domains in SCAP and HMG CoA reductase.

61 REBP transgenics and decreased expression in SCAP-deficient mice.

62 hamster ovary cells with a point mutation in SCAP (Y298C) that renders the protein resistant to inhib

63 A point mutation in SCAP(D443N) causes resistance to sterol suppression.

64 oduction of infectious virions is reduced in SCAP-depleted cells.

65 identify an important functional residue in SCAP, and they provide genetic evidence that the conform

66 Reexpression of SCAP in SCAP-deficient cells restored SREBP2 protein expression

67 n of the eight membrane-spanning segments in SCAP is consistent with the model proposed for HMG-CoA r

68 ols such as 25-hydroxycholesterol inactivate SCAP, suppressing SREBP proteolysis and turning off chol

69 These inhibitors increased SCAP phosphorylation, SREBP2 activation, and subsequent

70 by concomitant overexpression of full-length SCAP.

71 as restored by overexpression of full-length SCAP.

72 After modification, SCAP returns to the ER, as indicated by experiments that

73 Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to st

74 In transfected hamster cells, mutant SCAP in which Asp-428 is replaced by alanine (D428A) rem

75 produced transgenic mice that express mutant SCAP(D443N) in liver.

76 As a result, mutant SCAP failed to dissociate from Insigs, and it failed to

77 traced to a G-->A transition at codon 443 of SCAP, changing aspartic acid to asparagine.

78 enhances the cleavage-stimulating ability of SCAP and renders it resistant to inhibition by sterols.

79 avage of SREBPs by modulating the ability of SCAP to transport SREBPs to a post-ER compartment that h

80 In the absence of SCAP, the site 1 protease fails to cleave SREBPs, and th

81 ess SREBP cleavage by blocking the action of SCAP, thereby decreasing cholesterol synthesis.

82 ting mutation that increases the activity of SCAP and renders it resistant to inhibition by 25-hydrox

83 In sterol-overloaded cells, the activity of SCAP is blocked, SREBPs remain bound to membranes, and t

84 The activity of SCAP is inhibited by sterols, which appear to interact w

85 n of SCAP, prevent sterol-induced binding of SCAP to insig proteins and abolish feedback regulation o

86 Sterols induce binding of SCAP to INSIG-1, as determined by blue native-PAGE, and

87 Sterols also fail to induce binding of SCAP(L315F) to insig-1 or insig-2, two proteins that fun

88 lize the sterol-regulated step to budding of SCAP from ER and provide a system for biochemical dissec

89 monstrate that the N-linked carbohydrates of SCAP are modified by Golgi enzymes in sterol-depleted ce

90 ry cells the N-linked carbohydrate chains of SCAP were mostly in the endoglycosidase H-sensitive form

91 de genetic evidence that the conformation of SCAP dictates the rate of cholesterol synthesis in anima

92 avage assay to show that the conformation of SCAP is altered in vitro by addition of cholesterol to E

93 hat sterols act by inhibiting the cycling of SCAP between the ER and Golgi.

94 his is, in part, the result of a decrease of SCAP.

95 ere, we produced a conditional deficiency of SCAP in mouse liver by genomic recombination mediated by

96 rts the proliferation and differentiation of SCAP.

97 f a complex with the COOH-terminal domain of SCAP and that SCAP is therefore a required element in th

98 We show that the membrane domain of SCAP is a tetramer and that cholesterol binding is inhib

99 s also found in the sterol-sensing domain of SCAP, another protein that binds to Insigs in a sterol-s

100 The COOH-terminal domain of SCAP, like that of the SREBPs, is located on the cytosol

101 ns, each within the sterol-sensing domain of SCAP, prevent sterol-induced binding of SCAP to insig pr

102 teract with the polytopic membrane domain of SCAP.

103 cting with the membrane attachment domain of SCAP.

104 sterol cross-links to the membrane domain of SCAP.

105 The membrane-spanning domains of SCAP and HMG-CoA reductase confer sterol sensitivity upo

106 gy of the eight membrane-spanning domains of SCAP.

107 accumulation in membranes blocks the exit of SCAP from the ER, preventing SREBP cleavage and reducing

108 Two mutant forms of SCAP (Y298C and D443N) that are refractory to sterol reg

109 s that show that the Golgi-modified forms of SCAP cofractionate with ER membranes on density gradient

110 Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs.

111 COPII proteins that support incorporation of SCAP as well as VSVG into vesicles.

112 in vitro system to measure incorporation of SCAP into ER vesicles.

113 Sterols selectively block incorporation of SCAP into these vesicles without blocking incorporation

114 nd this is correlated with the inhibition of SCAP exit from the ER.

115 Golgi modifications of SCAP are restored when sterol-overloaded cells are treat

116 overloaded cells, the Golgi modifications of SCAP do not occur, apparently because SCAP fails to leav

117 sociation with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activ

118 the scaffold supported the proliferation of SCAP throughout the scaffold with differentiation into o

119 EBP actively prevents premature recycling of SCAP-SREBP until initiation of SREBP cleavage.

120 Thus, reduction of SCAP and the consequent suppression of cholesterol synth

121 of Scap in the brain show a 60% reduction of SCAP protein and ~30% reduction in brain cholesterol syn

122 Reexpression of SCAP in SCAP-deficient cells restored SREBP2 protein exp

123 67 amino acid octahelical membrane region of SCAP.

124 the polytopic membrane attachment region of SCAP.

125 25-hydroxycholesterol, a potent regulator of SCAP in vivo, fails to change SCAP's conformation in vit

126 nic responses, confirming the requirement of SCAP-SREBP2 in steroidogenesis.

127 hese effectors: they promote ER retention of SCAP, but ubiquitin-mediated degradation of HMGR.

128 acilitating sterol-dependent ER retention of SCAP, INSIG-1 plays a central role in cholesterol homeos

129 n 9) knockout approaches to test the role of SCAP in steroidogenesis.

130 ction techniques to overexpress a segment of SCAP containing transmembrane helices 1-6 in hamster and

131 The NH(2)-terminal segment of SCAP contains eight transmembrane helices, five of which

132 e that the NH2 terminus and COOH terminus of SCAP face the cytosol.

133 that IL-1beta increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum (ER) to

134 chanisms regulating ER-to-Golgi transport of SCAP-SREBP are understood in molecular detail, but littl

135 show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essent

136 s revealed the presence of a mutation in one SCAP allele that results in substitution of a conserved

137 d COOH-terminal domains of either SREBP-2 or SCAP disrupted the complex between full-length SREBP-2 a

138 he COOH-terminal domain of either SREBP-2 or SCAP, indicating that the complex forms between the two

139 no effect in cells expressing SCAP(D443N) or SCAP(Y298C).

140 om human dental pulp (DPSC), apical papilla (SCAP) and follicle (DFSC) during this study.

141 Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neu

142 ls (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs).

143 including stem cells of the apical papilla (SCAP), into the root canal system.

144 ified homologs of SREBP, its binding partner SCAP, and the ER retention protein Insig in Schizosaccha

145 7)), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11.

146 dicting severe community-acquired pneumonia (SCAP) and evaluate a health-services definition for SCAP

147 logy of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a

148 In vitro, BCMP (bone chip mass population), SCAP (stem cells from apical papilla), and SHED (stem ce

149 The IDSA/ATS 2007 minor criteria predicted SCAP with an area under the curve of 0.88 (95% confidenc

150 The polytopic membrane protein SCAP transports sterol regulatory element-binding protei

151 egions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-Co

152 protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductas

153 protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound

154 domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP comple

155 proteins SREBP cleavage-activating protein (SCAP) and HMG-CoA reductase (HMGR) both possess SSDs req

156 y binding SREBP cleavage-activating protein (SCAP) and preventing it from escorting SREBPs to the Gol

157 an intact SREBP cleavage-activating protein (SCAP) pathway.

158 binding protein cleavage activating protein (SCAP) revealed that the PS1-SCAP TMD4 mutant failed to c

159 SREBP cleavage-activating protein (SCAP) stimulates the proteolytic cleavage of membrane-bo

160 requires SREBP cleavage-activating protein (SCAP) to escort SREBP from the endoplasmic reticulum (ER

161 alysis of SREBP cleavage-activating protein (SCAP) transcripts from SRD-5 cells revealed the presence

162 ulated by SREBP cleavage-activating protein (SCAP), a membrane protein containing a sterol-sensing do

163 SREBP cleavage activating protein (SCAP), a membrane-bound glycoprotein, regulates the prot

164 pend upon SREBP cleavage-activating protein (SCAP), a polytopic endoplasmic reticulum membrane protei

165 ockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SR

166 diated by SREBP cleavage-activating protein (SCAP), a regulatory protein that activates S1P and also

167 protein (SREBP) cleavage-activating protein (SCAP), a sterol-sensing protein that escorts SREBPs.

168 protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription fac

169 protein (SREBP) cleavage activating protein (SCAP), and SREBP-2.

170 ctase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, th

171 change in SREBP cleavage-activating protein (SCAP), as revealed by the appearance of a new fragment i

172 pended on SREBP cleavage-activating protein (SCAP), because knocking down SCAP by RNA interference (R

173 e lacking SREBP cleavage-activating protein (SCAP), in which all nuclear SREBPs are absent.

174 and trap SREBP cleavage-activating protein (SCAP), retaining it in the ER and preventing it from esc

175 domain of SREBP cleavage-activating protein (SCAP), retaining the SCAP/SREBP complex in the ER and pr

176 In the SREBP cleavage-activating protein (SCAP), sterols inhibit the protein's activity through th

177 domain of SREBP cleavage-activating protein (SCAP), suggesting that both proteins bind to the same si

178 rm of the SREBP cleavage-activating protein (SCAP), which facilitates activation of endogenous SREBPs

179 ulated by SREBP cleavage-activating protein (SCAP), which forms complexes with SREBPs in membranes of

180 ibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation.

181 -encoding SREBP cleavage-activating protein (SCAP), which regulates cholesterol metabolism by stimula

182 of the SREBP-1c cleavage-activating protein (SCAP)-SREBP-1c complex for the Sec23/24 proteins of the

183 levels of SREBP cleavage-activating protein (SCAP).

184 binding protein cleavage-activating protein (SCAP).

185 encoding SREBP cleavage-activating protein (SCAP).

186 esignated SREBP cleavage-activating protein (SCAP).

187 esignated SREBP cleavage-activating protein (SCAP).

188 ty of the SREBP cleavage-activating protein (SCAP).SREBP-1c complex for coatomer protein complex II (

189 nt of the SREBP cleavage-activating protein (SCAP)/SREBP complex from endoplasmic reticulum (ER) to G

190 plex with SREBP cleavage activation protein (SCAP).

191 ew insights into how an integral ER protein, SCAP, mediates this process.

192 membranes requires a sterol-sensing protein, SCAP, which forms a complex with SREBPs.

193 sterol regulation of the mammalian proteins SCAP (SREBP cleavage activating protein) and HMG-CoA red

194 ivating protein (SCAP) revealed that the PS1-SCAP TMD4 mutant failed to coimmunoprecipitate endogenou

195 Using recombinant SCAP purified in detergent, we show that cholesterol act

196 SREBP regulates SCAP in human cells and yeast, indicating that this is a

197 ATF6 processing did not require SCAP, which is essential for SREBP processing.

198 ulate nSREBP levels by binding and retaining SCAP in the ER.

199 The sterol sensor SCAP is a key regulator of SREBP-2, the major transcript

200 erpret these data to indicate that the SREBP.SCAP complex directs the Site-1 protease to its target i

201 in transfected cells to show that the SREBP.SCAP complex is essential for Site-1 cleavage.

202 Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing

203 that glucose activates SREBP by stabilizing SCAP, a central regulator of the SREBP pathway.

204 Targeting SCAP N-glycosylation may provide a promising means of tr

205 th the COOH-terminal domain of SCAP and that SCAP is therefore a required element in the regulation o

206 We conclude that SCAP(D443N) stimulates proteolytic processing of native

207 Our results demonstrate that SCAP is required for progesterone production induced by

208 Here, we have demonstrated that SCAP Golgi-to-ER transport requires cleavage of SREBP at

209 These data provide in vivo evidence that SCAP and the SREBPs are required for hepatic lipid synth

210 mRNA microarray data indicated that SCAP influenced two major gene networks, one regulating

211 ation in all three cell lines indicates that SCAP may be unique in its ability to stimulate SREBP cle

212 ionic amphiphiles raise the possibility that SCAP may monitor specifically the composition of the cyt

213 These results provide formal proof that SCAP is essential for the cleavage of SREBPs at site 1.

214 Co-immunoprecipitation experiments show that SCAP and SREBP-2 form a complex that can be precipitated

215 In the present studies we show that SCAP, like the SREBPs, is located in membranes of the en

216 Through immunoisolation, we show that SCAP-containing vesicles, formed in vitro, also contain

217 The SCAP(TM1-6) segment competes with the SCAP.SREBP complex

218 The SCAP.SREBP complex is retained in the ER by Insig protei

219 tes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins and subsequent

220 tified as ER resident proteins that bind the SCAP/SREBP complex and promote its ER retention when cel

221 findings to indicate that sterols cause the SCAP.SREBP complex to bind to an ER retention protein th

222 is domain responds to sterols by causing the SCAP.SREBP complex to be retained in the ER, preventing

223 man cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point.

224 ions in two highly conserved residues in the SCAP sterol sensor have been identified that confer resi

225 ve retention protein, thereby liberating the SCAP.SREBP complex so that it can move to the Golgi desp

226 ER retention signal KDEL to S1P obviates the SCAP requirement and renders cleavage insensitive to ste

227 from a G-to-A transition in codon 443 of the SCAP gene, changing aspartic acid to asparagine.

228 ings were demonstrated in almost half of the SCAP patients.

229 ntion proteins that abrogate movement of the SCAP.SREBP complex to the Golgi apparatus where SREBPs a

230 a protein leads to an enhanced export of the SCAP.SREBP-1c complex from ER to the Golgi.

231 tion of Insig-2a promotes association of the SCAP.SREBP-1c complex with COPII vesicles and subsequent

232 tein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER.

233 Deletion of the SCAP/SREBP pathway in respiratory epithelial cells alter

234 these processes, including activation of the SCAP/SREBP pathway.

235 age-activating protein (SCAP), retaining the SCAP/SREBP complex in the ER and preventing it from movi

236 effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the micr

237 Thus, the SCAP-mediated mechanism for SREBP cleavage is utilized b

238 his regulated carbohydrate processing to the SCAP-regulated proteolysis of SREBP remains to be explor

239 The SCAP(TM1-6) segment competes with the SCAP.SREBP complex for binding to this putative retentio

240 Sterols act through SCAP's sterol-sensing domain by an obscure mechanism.

241 Thus, SCAP acts as key glucose-responsive protein linking onco

242 t binding of the COPII proteins Sec 23/24 to SCAP.

243 ment-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-reg

244 Whereas insig-1 binding to SCAP leads to ER retention, insig-1 binding to HMG CoA r

245 Direct binding of cholesterol to SCAP in intact cells was demonstrated by showing that a

246 In contrast to SCAP, the sterol sensor mutations had different affects

247 g synthesis of special vesicles dedicated to SCAP, or whether sterols block SCAP incorporation into c

248 Sterol-induced binding of Insigs to SCAP prevents the proteolytic processing of SREBPs, memb

249 Reductions in SREBP cleavage lead to SCAP degradation in lysosomes, providing additional nega

250 d derivative of 25-HC does not cross-link to SCAP.

251 rt is blocked by cholesterol, which triggers SCAP, the SREBP escort protein, to bind to Insigs, which

252 Wild-type SCAP, when overexpressed by transfection, stimulates the

253 Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years

254 This block is abolished when SCAP(TM1-6) contains a point mutation (Y298C) that is kn

255 n of cholesterol biosynthetic genes, whereas SCAP deficiency largely prevented these effects.

256 more carbonate-substituted mineral and with SCAP, SHED, and GF cells creating a less crystalline mat

257 SREBPs exit the ER in a complex with SCAP.

258 nus prevents the formation of complexes with SCAP and simultaneously reduces proteolytic cleavage.

259 e data imply that cholesterol interacts with SCAP directly by inducing it to bind to Insigs, whereas

260 This segment does not interfere with SCAP.SREBP movement to the Golgi in the absence of stero

261 by modulating SREBP processing jointly with SCAP.