TY - JOUR
T1 - cAMP response element-binding protein-binding protein mediates thyrotropin-releasing hormone signaling on thyrotropin subunit genes
AU - Hashimoto, Koshi
AU - Zanger, Kerstin
AU - Hollenberg, Anthony N.
AU - Cohen, Laurie E.
AU - Radovick, Sally
AU - Wondisford, Fredric E.
PY - 2000/10/27
Y1 - 2000/10/27
N2 - Transcription of pituitary α-glycoprotein hormone subunit (α-GSU) and thyrotropin β subunit (TSH-β) genes is stimulated by thyrotropin-releasing hormone (TRH). Since cAMP response element-binding protein (CREB)-binding protein (CBP) integrates a number of cell signaling pathways, we investigated whether CBP is important for TRH stimulation of the TSH subunit genes. Cotransfection of E1A in GH3 cells completely blocked TRH stimulation of the TSH subunit genes, suggesting that CBP is a key factor for TRH signaling in the pituitary. CBP and Pit-1 acted synergistically in TRH stimulation of the TSH-β promoter, and amino acids 1-450 of CBP were sufficient for the TRH effect. In contrast, on the human α-GSU promoter, CREB and P-Lim mediated TRH signaling. Intriguingly, CREB was phosphorylated upon TRH stimulation, leading to CBP recruitment to the α-GSU promoter. CBP also interacted with P-Lim in a TRH-dependent manner, suggesting that P-Lim is an important factor for non-cAMP response element-mediated TRH stimulation of this promoter. Distinct domains of CBP were required for TRH signaling by CREB and P-Lim on the α-GSU promoter, amino acids 450-700 and 1-450, respectively. Thus, the amino terminus of CBP plays a critical role in TRH signaling in the anterior pituitary via both Pit-1-dependent and -independent pathways, yielding differential regulation of pituitary gene products.
AB - Transcription of pituitary α-glycoprotein hormone subunit (α-GSU) and thyrotropin β subunit (TSH-β) genes is stimulated by thyrotropin-releasing hormone (TRH). Since cAMP response element-binding protein (CREB)-binding protein (CBP) integrates a number of cell signaling pathways, we investigated whether CBP is important for TRH stimulation of the TSH subunit genes. Cotransfection of E1A in GH3 cells completely blocked TRH stimulation of the TSH subunit genes, suggesting that CBP is a key factor for TRH signaling in the pituitary. CBP and Pit-1 acted synergistically in TRH stimulation of the TSH-β promoter, and amino acids 1-450 of CBP were sufficient for the TRH effect. In contrast, on the human α-GSU promoter, CREB and P-Lim mediated TRH signaling. Intriguingly, CREB was phosphorylated upon TRH stimulation, leading to CBP recruitment to the α-GSU promoter. CBP also interacted with P-Lim in a TRH-dependent manner, suggesting that P-Lim is an important factor for non-cAMP response element-mediated TRH stimulation of this promoter. Distinct domains of CBP were required for TRH signaling by CREB and P-Lim on the α-GSU promoter, amino acids 450-700 and 1-450, respectively. Thus, the amino terminus of CBP plays a critical role in TRH signaling in the anterior pituitary via both Pit-1-dependent and -independent pathways, yielding differential regulation of pituitary gene products.
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U2 - 10.1074/jbc.M006819200
DO - 10.1074/jbc.M006819200
M3 - Article
C2 - 10931853
AN - SCOPUS:0034721792
SN - 0021-9258
VL - 275
SP - 33365
EP - 33372
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -