Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 14 November 2006
Vol. 2006, Issue 361, p. tw388
[DOI: 10.1126/stke.3612006tw388]


Steroid Hormones Converging on the Promoter

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

Steroid hormones modulate gene transcription through interactions of their receptors with hormone-responsive elements on target genes. Noting that steroid receptors also activate the extracellular signal-regulated kinase (ERK) signaling pathway, Vicent et al. used the T47D-MTVL breast cancer cell line--which carries a chromosomally integrated copy of the luciferase gene under the control of the MMTV-LTR promoter--to investigate the role of ERK signaling in progestin action. Treatment with the progesterone receptor (PR) agonist R5020 led to rapid phosphorylation of ERK1/2, the progesterone receptor-B isoform (PRB), and the ERK target MSK1 (mitogen- and stress-activated protein kinase 1) as well as to transcriptional activation of the MMTV reporter. Hormone-dependent phosphorylation of PR and MSK1 required ERK activation, as did the hormone-dependent induction of MMTV (which also required MSK1 activation) and other progesterone target genes. R5020 stimulated recruitment to the MMTV promoter of PR and a complex containing phosphorylated PRB, phosphorylated ERK, and phosphorylated MSK1. Furthermore, R5020 elicited a MSK1-dependent increase in phosphorylation on serine 10 of histone H3 of the MMTV promoter, associated with the MSK1-dependent loss of HP1{gamma} (heterochromatin protein 1{gamma}) and recruitment of chromatin-remodeling factors and RNA polymerase II. Thus, activation of the ERK signaling pathway appears to play a critical role in progestin-dependent gene transcription that involves MSK1-dependent phosphorylation of histone H3, enabling the loss of repressive complexes from the promoters of target genes and the recruitment of chromatin-remodeling factors.

G. P. Vicent, C. Ballaré, A. S. Nacht, J. Clausell, A. Subtil-Rodríguez, I. Quiles, A. Jordan, M. Beato, Induction of progesterone target genes requires activation of Erk and Msk kinases and phosphorylation of histone H3. Mol. Cell. 24, 367-381 (2006). [PubMed]

Citation: E. M. Adler, Converging on the Promoter. Sci. STKE 2006, tw388 (2006).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882