TY - JOUR
T1 - A novel mechanism for cyclic adenosine 3',5'-monophosphate regulation of gene expression by CREB-binding protein
AU - Zanger, Kerstin
AU - Cohen, Laurie E.
AU - Hashimoto, Koshi
AU - Radovick, Sally
AU - Wondisford, Fredric E.
PY - 1999
Y1 - 1999
N2 - The pituitary-specific transcription factor, Pit-1, is necessary to mediate protein kinase A (PKA) regulation of the GH, PRL, and TSH-β subunit genes in the pituitary. Since these target genes lack classical cAMP DNA response elements (CREs), the mechanism of this regulation was previously unknown. We show that CREB binding protein (CBP), through two cysteine- histidine rich domains (C/H1 and C/H3), specifically and constitutively interacts with Pit-1 in pituitary cells. Pit-1 and CBP synergistically activate the PRL gene after PKA stimulation in a mechanism requiring both an intact Pit-1 amino-terminal and DNA-binding domain. A CBP construct containing the C/H3 domain [amino acids (aa) 1678-2441], but not one lacking the C/H3 domain (aa 1891-2441), is sufficient to mediate this response. Neither construct augments PKA regulation of CRE-containing promoters. Fusion of either CBP fragment to the GAL4 DNA-binding domain transferred complete PKA regulation to a heterologous promoter. These findings provide a mechanism for CREB-independent regulation of gene expression by cAMP.
AB - The pituitary-specific transcription factor, Pit-1, is necessary to mediate protein kinase A (PKA) regulation of the GH, PRL, and TSH-β subunit genes in the pituitary. Since these target genes lack classical cAMP DNA response elements (CREs), the mechanism of this regulation was previously unknown. We show that CREB binding protein (CBP), through two cysteine- histidine rich domains (C/H1 and C/H3), specifically and constitutively interacts with Pit-1 in pituitary cells. Pit-1 and CBP synergistically activate the PRL gene after PKA stimulation in a mechanism requiring both an intact Pit-1 amino-terminal and DNA-binding domain. A CBP construct containing the C/H3 domain [amino acids (aa) 1678-2441], but not one lacking the C/H3 domain (aa 1891-2441), is sufficient to mediate this response. Neither construct augments PKA regulation of CRE-containing promoters. Fusion of either CBP fragment to the GAL4 DNA-binding domain transferred complete PKA regulation to a heterologous promoter. These findings provide a mechanism for CREB-independent regulation of gene expression by cAMP.
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U2 - 10.1210/me.13.2.268
DO - 10.1210/me.13.2.268
M3 - Article
C2 - 9973256
AN - SCOPUS:0032927943
SN - 0888-8809
VL - 13
SP - 268
EP - 275
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 2
ER -