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

被引:83
作者
Chin, KT
Zhou, HJ
Wong, CM
Lee, JMF
Chan, CP
Qiang, BQ
Yuan, JG
Ng, IOL
Jin, DY
机构
[1] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Pathol, Fac Med, Hong Kong, Hong Kong, Peoples R China
[3] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China
[4] Peking Union Med Coll, Beijing 100005, Peoples R China
关键词
D O I
10.1093/nar/gki332
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:1859 / 1873
页数:15
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