The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma.
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.
Chin
King-Tung
KT
Department of Biochemistry, University of Hong Kong Hong Kong, China.
Zhou
Hai-Jun
HJ
Wong
Chun-Ming
CM
Lee
Joyce Man-Fong
JM
Chan
Ching-Ping
CP
Qiang
Bo-Qin
BQ
Yuan
Jian-Gang
JG
Ng
Irene Oi-lin
IO
Jin
Dong-Yan
DY
D051702:Activating Transcription Factor 6; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D020218:Response Elements; D014157:Transcription Factors / Q000032:analysis / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000242:Cyclic AMP; D019764:Phosphoenolpyruvate Carboxykinase (ATP)