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Down-regulation of estrogen receptor alpha (ER alpha) transcriptional activity by p27 is mediated by inhibition of ERa alpha nuclear localization and modulation of the ER alpha transcriptional complex

Title
Down-regulation of estrogen receptor alpha (ER alpha) transcriptional activity by p27 is mediated by inhibition of ERa alpha nuclear localization and modulation of the ER alpha transcriptional complex
Author
신인철
Keywords
BRCA1; Cell cycle; Cyclin D; Estrogen receptor; p27; Transcription
Issue Date
2012-12
Publisher
Elsevier
Citation
Cellular Signalling, 2012, 24(12), P.2249-2258
Abstract
To investigate the role of p27 on estrogen receptor (ER)a-mediated transcription, we generated MCF-7 cells with knocked down p27 via retroviral delivery of p27 shRNA. Suppression of p27 expression in MCF-7 cells resulted in up-regulation of ER alpha-mediated transcription by estradiol compared to the levels in control MCF-7 cells. Accordingly, transient transfection studies in 293T cells revealed that overexpression of p27 reduced ER alpha-mediated transcription. The effect of p27 on ER alpha transcriptional activity was independent of cell cycle arrest by p27, as cell cycle arrest induced by serum starvation did not significantly affect ER alpha-mediated transcription. Further, we observed that p27 inhibited nuclear localization of ER alpha, and that p27 was associated with ER alpha in the cytoplasm. We also investigated the role of p27 in the modulation of ER alpha transcriptional activity in the nucleus. We found that p27 negatively modulated ERa transcriptional activity by inhibiting association of cyclin D1 with ERa and recruiting BRCA1 to ER alpha transcriptional complex. Taken together, these data suggest that p27 inhibits ER alpha transcriptional activity by two independent mechanisms, namely, physical nuclear exclusion of ER alpha, and modulation of the ERa transcriptional complex. (c) 2012 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0898656812002070?via%3Dihub
ISSN
0898-6568
DOI
10.1016/j.cellsig.2012.07.011
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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