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Relative roles of CCAAT/enhancer-binding protein beta and cAMP regulatory element-binding protein in controlling transcription of the gene for phosphoenolpyruvate carboxykinase (GTP)
The gene for phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is expressed in a tissue-specific manner in the liver, kidney, and adipose tissue and is regulated by hormones including cAMP and insulin. Previous studies have shown that the CCAAT/enhancer-binding protein alpha (C/EBP alpha...
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Published in: | The Journal of biological chemistry 1993-01, Vol.268 (1), p.613-619 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The gene for phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is expressed in a tissue-specific manner in the
liver, kidney, and adipose tissue and is regulated by hormones including cAMP and insulin. Previous studies have shown that
the CCAAT/enhancer-binding protein alpha (C/EBP alpha) binds to several sites on the PEPCK promoter and activates transcription
from the promoter in hepatoma cells. Here, we report that a second member of the C/EBP family, C/EBP beta, bound to the same
sites on the PEPCK promoter. However, C/EBP beta stimulated transcription primarily through the cAMP-responsive element (CRE),
which maps between positions -77 to -94, but not at the more 5'-binding sites. In addition, the nuclear factor-1 site, which
is immediately adjacent to the CRE in the PEPCK promoter, was also required for the full response of the promoter to cotransfected
C/EBP beta. In gel mobility assays, antibodies to both C/EBP beta and the cAMP regulatory element-binding protein (CREB),
but not to C/EBP alpha, "supershifted" DNA-protein complexes formed between a synthetic CRE oligomer and proteins prepared
from rat liver nuclei. C/EBP beta mRNA was expressed at low levels in both the periportal and pericentral regions of the liver
lobule, whereas expression of the gene for C/EBP alpha was confined to the pericentral region of the liver lobule. PEPCK gene
transcription is greatest in the periportal region of the liver. CREB also bound to the CRE and stimulated transcription of
a PEPCK-CAT vector in the presence of an expression vector for the catalytic subunit of protein kinase A. C/EBP beta and CREB
bound to the CRE with similar affinities, both of which were greater than the affinity of C/EBP alpha. Within 90 min after
the administration of dibutyryl cAMP to rats, there was a marked increase in the hepatic concentration of C/EBP beta mRNA
and a decrease in the level of mRNA for C/EBP alpha. These studies indicate that C/EBP beta can regulate PEPCK gene transcription
by acting through the CRE and that C/EBP beta, together with CREB, may contribute to the cAMP responsiveness of the PEPCK
promoter. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)54195-8 |