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Nucleic Acids Research 2005 33(6):1859-1873; doi:10.1093/nar/gki332
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Published online 30 March 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma

King-Tung Chin1, Hai-Jun Zhou1,3, Chun-Ming Wong2, Joyce Man-Fong Lee2, Ching-Ping Chan1, Bo-Qin Qiang3, Jian-Gang Yuan3, Irene Oi-lin Ng2 and Dong-Yan Jin1,*

1Department of Biochemistry, University of Hong Kong Hong Kong, China 2Department of Pathology, Faculty of Medicine, University of Hong Kong Hong Kong, China 3National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100005, China

*To whom correspondence should be addressed at Department of Biochemistry, The University of Hong Kong, 3rd Floor, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong. Tel: +852 2819 9491; Fax: +852 2855 1254; Email: dyjin{at}hkucc.hku.hk

Received January 24, 2005. Revised March 5, 2005. Accepted March 14, 2005.

We have previously characterized transcription factor LZIP to be a growth suppressor targeted by hepatitis C virus oncoprotein. In search of proteins closely related to LZIP, we have identified a liver-enriched transcription factor CREB-H. LZIP and CREB-H represent a new subfamily of bZIP factors. CREB-H activates transcription by binding to cAMP responsive element, box B, and ATF6-binding element. Interestingly, CREB-H has a putative transmembrane (TM) domain and it localizes ambiently to the endoplasmic reticulum. Proteolytic cleavage that removes the TM domain leads to nuclear translocation and activation of CREB-H. CREB-H activates the promoter of hepatic gluconeogenic enzyme phosphoenolpyruvate carboxykinase. This activation can be further stimulated by cAMP and protein kinase A. CREB-H transcript is exclusively abundant in adult liver. In contrast, the expression of CREB-H mRNA is aberrantly reduced in hepatoma tissues and cells. The enforced expression of CREB-H suppresses the proliferation of cultured hepatoma cells. Taken together, our findings suggest that the liver-enriched bZIP transcription factor CREB-H is a growth suppressor that plays a role in hepatic physiology and pathology.

DDBJ/EMBL/GenBank accession no. AF392874


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