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 incorporation within ECM hydrogels did not impact u

7 SCAP knockdown in vascular smooth muscle cells alleviate

8 SCAP knockdown in VSMCs reduced oxidative stress and inc

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

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

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

12 SCAP-stimulated proteolysis releases active fragments of

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

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

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

16 gulation of Nos2/Arg1 ratio observed for all SCAP embedded hydrogels.

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

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

19 f the interaction between INSIG proteins and SCAP by sterol levels is critical for the dissociation o

20 s the interaction between INSIG proteins and SCAP, leading to the translocation of the SCAP-SREBP com

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

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

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

24 ned SCAP-O and separated SCAP-O(BCOR-WT) and SCAP-O(BCOR-mut) as verified by sequencing.

25 this mechanism, named secretion-coupled APA (SCAP), is also executed in B cell differentiation to pla

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

27 lesterol levels, but the association between SCAP and foam cell formation in vascular smooth muscle c

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

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

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

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

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

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

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

35 Breeding SCAP(flox/flox) mice with SM22alpha-Cre mice resulted in

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

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

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

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

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

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

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

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

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

45 By coupling SCAP to cross-linking mass spectrometry, an integrative

46 able offspring with the homozygote SM22-Cre: SCAP(flox/flox) genotype due to embryonic lethality.

47 We found that the heterozygote SM22alpha-Cre:SCAP(flox/+):ApoE(-/-) mice fed a Western diet for 12 wk

48 hagy in VSMCs was increased in SM22alpha-Cre:SCAP(flox/+):ApoE(-/-) mice.

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

50 M hydrogels are suitable vehicles to deliver SCAP due to their physical properties, preservation of S

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

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

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

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

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

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

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

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

59 transfected with expression vectors encoding SCAP.

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

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

62 nd evaluate a health-services definition for SCAP.

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

64 1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct tar

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

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

67 Further, SCAP cells were positive for alpha-SMA while they comple

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

69 with a fibrin hydrogel with or without human SCAP.

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

71 -2 also enhance the conformational change in SCAP that occurs upon addition of certain cationic amphi

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

73 cause a detectable conformational change in SCAP.

74 itro to produce the conformational change in SCAP.

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

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

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

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

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

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

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

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

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

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

85 by concomitant overexpression of full-length SCAP.

86 as restored by overexpression of full-length SCAP.

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

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

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

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

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

92 either normal (SCAP-O(BCOR-WT)) or mutated (SCAP-O(BCOR-mut)) BCOR transcripts.

93 a mixture of cells expressing either normal (SCAP-O(BCOR-WT)) or mutated (SCAP-O(BCOR-mut)) BCOR tran

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

111 rts the proliferation and differentiation of SCAP.

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

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

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

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

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

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

118 teract with the polytopic membrane domain of SCAP.

119 cting with the membrane attachment domain of SCAP.

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

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

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

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

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

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

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

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

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

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

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

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

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

133 o their physical properties, preservation of SCAP viability and immunomodulatory capacity.

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

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

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

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

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

139 67 amino acid octahelical membrane region of SCAP.

140 the polytopic membrane attachment region of SCAP.

141 25-hydroxycholesterol, a potent regulator of SCAP in vivo, fails to change SCAP's conformation in vit

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

157 gram stem cells from a tooth apical papilla (SCAP) of a patient with OFCD, termed SCAP-O, into iPSCs.

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

159 ental pulp (DPSC) and dental apical papilla (SCAP) to engineer pericyte-supported vascular capillarie

160 enchymal stem cells from the apical papilla (SCAP) to reduce local inflammation and provide a regener

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

176 proteins, SREBP cleavage-activating protein (SCAP) and sterols in the endoplasmic reticulum.

177 protein (SREBP) cleavage-activating protein (SCAP) is a cholesterol sensor that plays a critical role

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

204 binding protein cleavage-activating protein (SCAP).

205 encoding SREBP cleavage-activating protein (SCAP).

206 esignated SREBP cleavage-activating protein (SCAP).

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

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

209 plex with SREBP cleavage activation protein (SCAP).

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

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

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

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

214 scribe serial capture affinity purification (SCAP), in which two separate proteins are tagged with ei

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

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

217 We reprogrammed SCAP-O and subclone SCAP-O(BCOR-mut) into transgene-free

218 We found that after reprogramming SCAP-O or subclone SCAP-O(BCOR-mut) into iPSCs, some of

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

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

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

222 We subcloned SCAP-O and separated SCAP-O(BCOR-WT) and SCAP-O(BCOR-mut) as verified by sequ

223 Using tissue-specific SCAP knockdown in apolipoprotein E (ApoE)(-/-) mice, we

224 VSMC-specific SCAP knockdown decreased the lipid accumulation and intr

225 VSMC-specific SCAP knockdown mice were generated by Cre/LoxP-mediated

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

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

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

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

230 We reprogrammed SCAP-O and subclone SCAP-O(BCOR-mut) into transgene-free iPSCs using an exci

231 that after reprogramming SCAP-O or subclone SCAP-O(BCOR-mut) into iPSCs, some of the iPSC clones exp

232 The selected subclone SCAP-O(BCOR-mut) expressed only the mutated BCOR transcr

233 We subcloned SCAP-O and separated SCAP-O(BCOR-WT) and SCAP-O(BCOR-mut

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

235 apilla (SCAP) of a patient with OFCD, termed SCAP-O, into iPSCs.

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

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

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

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

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

241 Together, our data indicate that SCAP tailors the transcriptome during formation of secre

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

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

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

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

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

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

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

249 The SCAP-O carry a copy of the BCOR gene having 1 nucleotide

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

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

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

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

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

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

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

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

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

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

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

261 vels is critical for the dissociation of the SCAP-SREBP complex from the endoplasmic reticulum and th

262 nd SCAP, leading to the translocation of the SCAP-SREBP complex to the Golgi apparatus, the activatio

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

287 ion within ECM hydrogels did not impact upon SCAP immunoregulatory properties, with significant downr

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

289 Similarly, in vitro, SCAP knockdown in human coronary artery VSMCs by RNA int

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

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

292 sought to search the mechanism through which SCAP signaling affects VSMC foam cell development.

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

294 SREBPs exit the ER in a complex with SCAP.

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

296 on in a mechanism involving interaction with SCAP and PAQR3 and subsequent SREBP2-processing.

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

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

299 by modulating SREBP processing jointly with SCAP.

300 Tnf expression was reduced with SCAP embedded in B8, reflecting the gene expression obse