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Conference Paper: N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H

TitleN-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H
Authors
Issue Date2010
Citation
Hong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May 2010. How to Cite?
Abstract
CREB-H is a liver-enriched bZIP transcription factor of the CREB3 subfamily. CREB-H is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain. Aberrant expression of CREB-H is implicated in liver cancer. In this study we characterized N-linked glycosylation of CREB-H in the luminal domain at the C-terminus. We found that CREB-H is modified at three N-linked glycosylation sites in this region. Disruption of all three sites by site-directed mutagenesis completely abrogated N-linked glycosylation of CREB-H. The unglycosylated mutant of CREB-H was not unstable, unfolded or aggregated. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A and KDEL-tailed site 1 protease, unglycosylated or deglycosylated CREB-H was largely uncleaved, retained in an inactive form in the endoplasmic reticulum, and less capable of activating transcription driven by unfolded protein response element or C-reactive protein promoter. Taken together, our findings suggest that N-linked glycosylation is required for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for the regulation of CREB-H-dependent transcription.
DescriptionPlatform Presentations: T01
Persistent Identifierhttp://hdl.handle.net/10722/125961

 

DC FieldValueLanguage
dc.contributor.authorChan, CPen_HK
dc.contributor.authorMak, TYen_HK
dc.contributor.authorChin, KTen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorJin, DY-
dc.date.accessioned2010-10-31T12:01:53Z-
dc.date.available2010-10-31T12:01:53Z-
dc.date.issued2010en_HK
dc.identifier.citationHong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May 2010.en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125961-
dc.descriptionPlatform Presentations: T01-
dc.description.abstractCREB-H is a liver-enriched bZIP transcription factor of the CREB3 subfamily. CREB-H is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain. Aberrant expression of CREB-H is implicated in liver cancer. In this study we characterized N-linked glycosylation of CREB-H in the luminal domain at the C-terminus. We found that CREB-H is modified at three N-linked glycosylation sites in this region. Disruption of all three sites by site-directed mutagenesis completely abrogated N-linked glycosylation of CREB-H. The unglycosylated mutant of CREB-H was not unstable, unfolded or aggregated. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A and KDEL-tailed site 1 protease, unglycosylated or deglycosylated CREB-H was largely uncleaved, retained in an inactive form in the endoplasmic reticulum, and less capable of activating transcription driven by unfolded protein response element or C-reactive protein promoter. Taken together, our findings suggest that N-linked glycosylation is required for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for the regulation of CREB-H-dependent transcription.-
dc.languageengen_HK
dc.relation.ispartofHong Kong Inter-University Biochemistry Postgraduate Symposium-
dc.subject.meshAnimals-
dc.subject.meshBrefeldin A - pharmacology-
dc.subject.meshCell Membrane - drug effects - metabolism-
dc.subject.meshCyclic AMP Response Element-Binding Protein - chemistry - genetics - metabolism-
dc.subject.meshProtein Processing, Post-Translational - drug effects-
dc.titleN-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-Hen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9533&volume=123, pt. 9&spage=1438&epage=1448&date=2010&atitle=N-linked+glycosylation+is+required+for+optimal+proteolytic+activation+of+membrance-bound+transcription+factor+CREB-H-
dc.identifier.emailChan, CP: cpchan@HKUCC.hku.hken_HK
dc.identifier.emailMak, TY: h0326222@hkusua.hku.hk-
dc.identifier.emailChin, KT: tonychin@hkusua.hku.hk-
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hk-
dc.identifier.emailJin, DY: dyjin@hkucc.hku.hk-
dc.identifier.hkuros182882en_HK
dc.identifier.hkuros193224-

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