TY - JOUR
T1 - CREB binding protein recruitment to the transcription complex requires growth factor-dependent phosphorylation of its GF box
AU - Zanger, Kerstin
AU - Radovick, Sally
AU - Wondisford, Fredric E.
N1 - Funding Information:
This research was supported by grants from the National Institutes of Health to S. R. and F. E. W. as well as a postdoctoral research award from the Deutsche Forschungsgemeinschaft to K. Z.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - Growth factors such as epidermal growth factor (EGF) and insulin regulate development and metabolism via genes containing both POU homeodomain (Pit-1) and phorbol ester (AP-1) response elements. Although CREB binding protein (CBP) functions as a coactivator on these elements, the mechanism of transactivation was previously unclear. We now demonstrate that CBP is recruited to these elements only after it is phosphorylated at serine 436 by growth factor-dependent signaling pathways. In contrast, p300, a protein closely related to CBP that lacks this phosphorylation site, binds only weakly to the transcription complex and in a growth factor-independent manner. A small region of CBP (amino acids 312-440), which we term GF box, contains a potent transactivation domain and mediates this effect. Direct phosphorylation represents a novel mechanism controlling coactivator recruitment to the transcription complex.
AB - Growth factors such as epidermal growth factor (EGF) and insulin regulate development and metabolism via genes containing both POU homeodomain (Pit-1) and phorbol ester (AP-1) response elements. Although CREB binding protein (CBP) functions as a coactivator on these elements, the mechanism of transactivation was previously unclear. We now demonstrate that CBP is recruited to these elements only after it is phosphorylated at serine 436 by growth factor-dependent signaling pathways. In contrast, p300, a protein closely related to CBP that lacks this phosphorylation site, binds only weakly to the transcription complex and in a growth factor-independent manner. A small region of CBP (amino acids 312-440), which we term GF box, contains a potent transactivation domain and mediates this effect. Direct phosphorylation represents a novel mechanism controlling coactivator recruitment to the transcription complex.
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U2 - 10.1016/S1097-2765(01)00202-7
DO - 10.1016/S1097-2765(01)00202-7
M3 - Article
C2 - 11463380
AN - SCOPUS:0035265684
SN - 1097-2765
VL - 7
SP - 551
EP - 558
JO - Molecular cell
JF - Molecular cell
IS - 3
ER -