Conference Paper: Requirement of N-linked glycosylation in the luminal domain for optimal proteolytic activation of liver-enriched transcription factor CREB-H
| Title | Requirement of N-linked glycosylation in the luminal domain for optimal proteolytic activation of liver-enriched transcription factor CREB-H |
|---|---|
| Authors | Chan, CP Mak, TY Chin, KT Jin, D |
| Issue Date | 2008 |
| Publisher | American Society for Cell Biology. The Conference's web site is located at http://www.ascb.org/ |
| Citation | The 48th Annual meeting of the American Society for Cell Biology (ASCB), San Francisco, USA, 13-17 December 2008. In Meeting Abstract p. 592 no. 2045/B510 [How to Cite?] |
| Abstract | CREB-H is a liver-enriched bZIP transcription factor closely related to CREB3. CREB-H is activated by intramembrane proteolysis that releases an N-terminal fragment. Aberrant expression of CREB-H is implicated in hepatocellular carcinoma. In this study we characterized N-linked glycosylation of CREB-H which occurs at three sites in the C-terminal luminal domain. When all three sites were disrupted by sitedirected mutagenesis, N-linked glycosylation of CREB-H was completely abrogated. The CREB-H mutants defective for N-linked glycosylation poorly activated transcription driven by unfolded protein response element or C-reactive protein promoter. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A, unglycosylated CREB-H remained largely uncleaved, anchored to the endoplasmic reticulum membrane, and unable to activate transcription. Taken together, our findings suggest that N-linked glycosylation is necessary for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for post-translational regulation of the CREB3 subfamily of membrane-associated transcription factors. |
| Description | Mechanism of Nuclear Transcription (2035 – 2056) Session: Poster Session 3: no. 2045/B510 |
| dc.contributor.author | Chan, CP |
|---|---|
| dc.contributor.author | Mak, TY |
| dc.contributor.author | Chin, KT |
| dc.contributor.author | Jin, D |
| dc.date.accessioned | 2011-09-23T06:06:32Z |
| dc.date.available | 2011-09-23T06:06:32Z |
| dc.date.issued | 2008 |
| dc.description.abstract | CREB-H is a liver-enriched bZIP transcription factor closely related to CREB3. CREB-H is activated by intramembrane proteolysis that releases an N-terminal fragment. Aberrant expression of CREB-H is implicated in hepatocellular carcinoma. In this study we characterized N-linked glycosylation of CREB-H which occurs at three sites in the C-terminal luminal domain. When all three sites were disrupted by sitedirected mutagenesis, N-linked glycosylation of CREB-H was completely abrogated. The CREB-H mutants defective for N-linked glycosylation poorly activated transcription driven by unfolded protein response element or C-reactive protein promoter. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A, unglycosylated CREB-H remained largely uncleaved, anchored to the endoplasmic reticulum membrane, and unable to activate transcription. Taken together, our findings suggest that N-linked glycosylation is necessary for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for post-translational regulation of the CREB3 subfamily of membrane-associated transcription factors. |
| dc.description | Mechanism of Nuclear Transcription (2035 – 2056) Session: Poster Session 3: no. 2045/B510 |
| dc.identifier.citation | The 48th Annual meeting of the American Society for Cell Biology (ASCB), San Francisco, USA, 13-17 December 2008. In Meeting Abstract p. 592 no. 2045/B510 [How to Cite?] |
| dc.identifier.hkuros | 193222 |
| dc.identifier.hkuros | 157415 |
| dc.identifier.uri | http://hdl.handle.net/10722/140096 |
| dc.language | eng |
| dc.publisher | American Society for Cell Biology. The Conference's web site is located at http://www.ascb.org/ |
| dc.publisher.place | United States |
| dc.relation.ispartof | Annual meeting of the American Society for Cell Biology |
| dc.title | Requirement of N-linked glycosylation in the luminal domain for optimal proteolytic activation of liver-enriched transcription factor CREB-H |
| dc.type | Conference_Paper |