Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016015510> ?p ?o ?g. }
- W2016015510 endingPage "31734" @default.
- W2016015510 startingPage "31726" @default.
- W2016015510 abstract "The regulation of lipid homeostasis by insulin is mediated in part by the enhanced transcription of the gene encoding sterol regulatory element-binding protein-1c (SREBP-1c). The nascent SREBP-1c is embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi where two sequential cleavages generate its NH(2)-terminal fragment, nSREBP-1c. We have shown recently that in primary cultures of rat hepatocytes, insulin rapidly and selectively stimulates proteolytic processing of the nascent SREBP-1c by enhancing the affinity of the SREBP cleavage-activating protein (SCAP).SREBP-1c complex for coatomer protein complex II (COPII) vesicles. The SCAP.SREBP complex is retained in the ER by Insig proteins. We report here that insulin persistently stimulates controlled proteolysis of the nascent SREBP-1c by selectively reducing the level of Insig-2a protein via accelerated degradation of its cognate mRNA. Insulin enhanced the rate of turnover of Insig-2a mRNA via its 3'-untranslated region. Insulin-induced depletion of Insig-2a promotes association of the SCAP.SREBP-1c complex with COPII vesicles and subsequent migration to the Golgi where site-1 and site-2 proteases process the nascent SREBP-1c. Consistent with this mechanism, experimental knockdown of Insig-2a expression with small interfering RNA mimicked insulin-induced proteolysis of the nascent SREBP-1c, whereas exogenous expression of Insig-2a in hepatocytes led to reduced intramembrane proteolysis of the newly synthesized SREBP-1c. The action of insulin on the processing of the nascent SREBP-1c via Insig-2a was highly selective, as proteolysis of the newly synthesized SREBP-2 remained unchanged under identical conditions. On the basis of these data, we propose that the stimulation of SREBP-1c processing by insulin is mediated by a selective depletion of Insig-2a protein by promoting decay of its cognate mRNA. Thus, insulin-induced reduction in Insig-2a protein leads to an enhanced export of the SCAP.SREBP-1c complex from ER to the Golgi." @default.
- W2016015510 created "2016-06-24" @default.
- W2016015510 creator A5024196507 @default.
- W2016015510 creator A5036558176 @default.
- W2016015510 creator A5038437206 @default.
- W2016015510 creator A5071649059 @default.
- W2016015510 creator A5075446190 @default.
- W2016015510 date "2009-11-01" @default.
- W2016015510 modified "2023-10-17" @default.
- W2016015510 title "Insulin Enhances the Biogenesis of Nuclear Sterol Regulatory Element-binding Protein (SREBP)-1c by Posttranscriptional Down-regulation of Insig-2A and Its Dissociation from SREBP Cleavage-activating Protein (SCAP)·SREBP-1c Complex" @default.
- W2016015510 cites W1611419331 @default.
- W2016015510 cites W1944789111 @default.
- W2016015510 cites W1970761589 @default.
- W2016015510 cites W1972698819 @default.
- W2016015510 cites W1979560290 @default.
- W2016015510 cites W1984662248 @default.
- W2016015510 cites W1992860556 @default.
- W2016015510 cites W1993243592 @default.
- W2016015510 cites W2000815833 @default.
- W2016015510 cites W2004920315 @default.
- W2016015510 cites W2005021452 @default.
- W2016015510 cites W2023719883 @default.
- W2016015510 cites W2030610610 @default.
- W2016015510 cites W2032261439 @default.
- W2016015510 cites W2053722014 @default.
- W2016015510 cites W2055315631 @default.
- W2016015510 cites W2057680047 @default.
- W2016015510 cites W2061841671 @default.
- W2016015510 cites W2073926725 @default.
- W2016015510 cites W2080664601 @default.
- W2016015510 cites W2086453930 @default.
- W2016015510 cites W2089086088 @default.
- W2016015510 cites W2097632838 @default.
- W2016015510 cites W2104360518 @default.
- W2016015510 cites W2110646266 @default.
- W2016015510 cites W2115420718 @default.
- W2016015510 cites W2117716768 @default.
- W2016015510 cites W2119390770 @default.
- W2016015510 cites W2135536111 @default.
- W2016015510 cites W2158465207 @default.
- W2016015510 cites W2168812832 @default.
- W2016015510 cites W4213101600 @default.
- W2016015510 doi "https://doi.org/10.1074/jbc.m109.050914" @default.
- W2016015510 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2797243" @default.
- W2016015510 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19759400" @default.
- W2016015510 hasPublicationYear "2009" @default.
- W2016015510 type Work @default.
- W2016015510 sameAs 2016015510 @default.
- W2016015510 citedByCount "88" @default.
- W2016015510 countsByYear W20160155102012 @default.
- W2016015510 countsByYear W20160155102013 @default.
- W2016015510 countsByYear W20160155102014 @default.
- W2016015510 countsByYear W20160155102015 @default.
- W2016015510 countsByYear W20160155102016 @default.
- W2016015510 countsByYear W20160155102017 @default.
- W2016015510 countsByYear W20160155102018 @default.
- W2016015510 countsByYear W20160155102019 @default.
- W2016015510 countsByYear W20160155102020 @default.
- W2016015510 countsByYear W20160155102021 @default.
- W2016015510 countsByYear W20160155102022 @default.
- W2016015510 countsByYear W20160155102023 @default.
- W2016015510 crossrefType "journal-article" @default.
- W2016015510 hasAuthorship W2016015510A5024196507 @default.
- W2016015510 hasAuthorship W2016015510A5036558176 @default.
- W2016015510 hasAuthorship W2016015510A5038437206 @default.
- W2016015510 hasAuthorship W2016015510A5071649059 @default.
- W2016015510 hasAuthorship W2016015510A5075446190 @default.
- W2016015510 hasBestOaLocation W20160155101 @default.
- W2016015510 hasConcept C104317684 @default.
- W2016015510 hasConcept C119062480 @default.
- W2016015510 hasConcept C158617107 @default.
- W2016015510 hasConcept C185592680 @default.
- W2016015510 hasConcept C206912223 @default.
- W2016015510 hasConcept C46617944 @default.
- W2016015510 hasConcept C55493867 @default.
- W2016015510 hasConcept C6492254 @default.
- W2016015510 hasConcept C85051948 @default.
- W2016015510 hasConcept C86339819 @default.
- W2016015510 hasConcept C86803240 @default.
- W2016015510 hasConcept C95444343 @default.
- W2016015510 hasConceptScore W2016015510C104317684 @default.
- W2016015510 hasConceptScore W2016015510C119062480 @default.
- W2016015510 hasConceptScore W2016015510C158617107 @default.
- W2016015510 hasConceptScore W2016015510C185592680 @default.
- W2016015510 hasConceptScore W2016015510C206912223 @default.
- W2016015510 hasConceptScore W2016015510C46617944 @default.
- W2016015510 hasConceptScore W2016015510C55493867 @default.
- W2016015510 hasConceptScore W2016015510C6492254 @default.
- W2016015510 hasConceptScore W2016015510C85051948 @default.
- W2016015510 hasConceptScore W2016015510C86339819 @default.
- W2016015510 hasConceptScore W2016015510C86803240 @default.
- W2016015510 hasConceptScore W2016015510C95444343 @default.
- W2016015510 hasIssue "46" @default.
- W2016015510 hasLocation W20160155101 @default.
- W2016015510 hasLocation W20160155102 @default.
- W2016015510 hasLocation W20160155103 @default.
- W2016015510 hasLocation W20160155104 @default.
- W2016015510 hasOpenAccess W2016015510 @default.