TY - JOUR
T1 - Down-regulation of the cyclin a promoter by transforming growth factor- β1 is associated with a reduction in phosphorylated activating transcription factor-1 and cyclic AMP-responsive element-binding protein
AU - Yoshizumi, Masao
AU - Wang, Hong
AU - Hsieh, Chung Ming
AU - Sibinga, Nicholas E.S.
AU - Perrella, Mark A.
AU - Lee, Mu En
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/8/29
Y1 - 1997/8/29
N2 - Transforming growth factor (TGF)-β1 prevents cell cycle progression by inhibiting several regulators, including cyclin A. To study the mechanisms by which TGF-β1 down-regulates cyclin A gene expression, we transfected reporter plasmids driven by the cyclin A promoter into mink lung epithelial cells in the absence and presence of TGF-β1. The TGF-β1-induced down- regulation of cyclin A promoter activity appeared to be mediated via the activating transcription factor (ATF) site, because mutation of this site abolished down-regulation. Surprisingly, although TGF-β1 treatment for 24 h markedly decreased cyclin A promoter activity, it did not decrease the abundance of the ATF-binding proteins ATF-1 and cyclic AMP-responsive binding protein (CREB). However, we detected 90 and 78% reductions (by Western analysis) in phosphorylated CREB and ATF-1, respectively, in mink lung epithelial cells treated with TGF-β1. TGF-β1-induced down-regulation of cyclin A promoter activity was reversed by okadaic acid (a phosphatase inhibitor) and by cotransfection with plasmids expressing the cAMP-dependent protein kinase catalytic subunit or the simian virus small tumor antigen (Sm- t, an inhibitor of PP2A). These data indicate that TGF-β1 may down-regulate cyclin A promoter activity by decreasing phosphorylation of CREB and ATF-1.
AB - Transforming growth factor (TGF)-β1 prevents cell cycle progression by inhibiting several regulators, including cyclin A. To study the mechanisms by which TGF-β1 down-regulates cyclin A gene expression, we transfected reporter plasmids driven by the cyclin A promoter into mink lung epithelial cells in the absence and presence of TGF-β1. The TGF-β1-induced down- regulation of cyclin A promoter activity appeared to be mediated via the activating transcription factor (ATF) site, because mutation of this site abolished down-regulation. Surprisingly, although TGF-β1 treatment for 24 h markedly decreased cyclin A promoter activity, it did not decrease the abundance of the ATF-binding proteins ATF-1 and cyclic AMP-responsive binding protein (CREB). However, we detected 90 and 78% reductions (by Western analysis) in phosphorylated CREB and ATF-1, respectively, in mink lung epithelial cells treated with TGF-β1. TGF-β1-induced down-regulation of cyclin A promoter activity was reversed by okadaic acid (a phosphatase inhibitor) and by cotransfection with plasmids expressing the cAMP-dependent protein kinase catalytic subunit or the simian virus small tumor antigen (Sm- t, an inhibitor of PP2A). These data indicate that TGF-β1 may down-regulate cyclin A promoter activity by decreasing phosphorylation of CREB and ATF-1.
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U2 - 10.1074/jbc.272.35.22259
DO - 10.1074/jbc.272.35.22259
M3 - Article
C2 - 9268374
AN - SCOPUS:0030772028
SN - 0021-9258
VL - 272
SP - 22259
EP - 22264
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -