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Conference Paper: N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H
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TitleN-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H
 
AuthorsChan, CP
Mak, TY
Chin, KT
Ng, IOL
Jin, DY
 
Issue Date2010
 
CitationHong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May 2010. [How to Cite?]
 
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.
 
DescriptionPlatform Presentations: T01
 
DC FieldValue
dc.contributor.authorChan, CP
 
dc.contributor.authorMak, TY
 
dc.contributor.authorChin, KT
 
dc.contributor.authorNg, IOL
 
dc.contributor.authorJin, DY
 
dc.date.accessioned2010-10-31T12:01:53Z
 
dc.date.available2010-10-31T12:01:53Z
 
dc.date.issued2010
 
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.descriptionPlatform Presentations: T01
 
dc.identifier.citationHong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May 2010. [How to Cite?]
 
dc.identifier.hkuros182882
 
dc.identifier.hkuros193224
 
dc.identifier.openurl
 
dc.identifier.urihttp://hdl.handle.net/10722/125961
 
dc.languageeng
 
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-H
 
dc.typeConference_Paper
 
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<item><contributor.author>Chan, CP</contributor.author>
<contributor.author>Mak, TY</contributor.author>
<contributor.author>Chin, KT</contributor.author>
<contributor.author>Ng, IOL</contributor.author>
<contributor.author>Jin, DY</contributor.author>
<date.accessioned>2010-10-31T12:01:53Z</date.accessioned>
<date.available>2010-10-31T12:01:53Z</date.available>
<date.issued>2010</date.issued>
<identifier.citation>Hong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May 2010.</identifier.citation>
<identifier.uri>http://hdl.handle.net/10722/125961</identifier.uri>
<description>Platform Presentations: T01</description>
<description.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.</description.abstract>
<language>eng</language>
<relation.ispartof>Hong Kong Inter-University Biochemistry Postgraduate Symposium</relation.ispartof>
<subject.mesh>Animals</subject.mesh>
<subject.mesh>Brefeldin A - pharmacology</subject.mesh>
<subject.mesh>Cell Membrane - drug effects - metabolism</subject.mesh>
<subject.mesh>Cyclic AMP Response Element-Binding Protein - chemistry - genetics - metabolism</subject.mesh>
<subject.mesh>Protein Processing, Post-Translational - drug effects</subject.mesh>
<title>N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H</title>
<type>Conference_Paper</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=0021-9533&amp;volume=123, pt. 9&amp;spage=1438&amp;epage=1448&amp;date=2010&amp;atitle=N-linked+glycosylation+is+required+for+optimal+proteolytic+activation+of+membrance-bound+transcription+factor+CREB-H</identifier.openurl>
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