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The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2005 Mar 30; Vol. 33 (6), pp. 1859-73. Date of Electronic Publication: 2005 Mar 30 (Print Publication: 2005). - Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- Activating Transcription Factor 6
Animals
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Cyclic AMP metabolism
Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins metabolism
Humans
Liver Neoplasms pathology
Mice
Molecular Sequence Data
Phosphoenolpyruvate Carboxykinase (ATP) genetics
Response Elements
Transcription Factors analysis
Transcription Factors classification
Transcription Factors physiology
Transcriptional Activation
Tumor Suppressor Proteins physiology
Carcinoma, Hepatocellular metabolism
Liver metabolism
Liver Neoplasms metabolism
Transcription Factors metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 15800215
- Full Text :
- https://doi.org/10.1093/nar/gki332