Progesterone regulates transcription of the p21(WAF1) cyclin- dependent kinase inhibitor gene through Sp1 and CBP/p300.

The Journal of Biological Chemistry
G OwenKathryn B Horwitz

Abstract

Progesterone has biphasic effects on proliferation of breast cancer cells; it stimulates growth in the first cell cycle, then arrests cells at G1/S of the second cycle accompanied by up-regulation of the cyclin-dependent kinase inhibitor, p21. We now show that progesterone regulates transcription of the p21 promoter by an unusual mechanism. This promoter lacks a canonical progesterone response element. Instead, progesterone receptors (PRs) interact with the promoter through the transcription factor Sp1 at the third and fourth of six Sp1 binding sites located downstream of nucleotide 154. Mutation of Sp1 site 3 eliminates basal transcription, and mutation of sites 3 and 4 eliminates transcriptional up-regulation by progesterone. Progesterone-mediated transcription is further prevented by overexpression of E1A, suggesting that CBP/p300 is required. Indeed, in HeLa cells, Sp1 and CBP/p300 associate with stably integrated flag-tagged PRs in a multiprotein complex. Since many signals converge on p21, cross-talk between PRs and other factors co-localized on the p21 promoter, may explain how progesterone can be either proliferative or differentiative in different target cells.

References

May 1, 1990·Endocrine Reviews·C L Clarke, R L Sutherland
Nov 3, 1989·Science·A B Pardee
Sep 15, 1995·Genes & Development·J P LydonB W O'Malley
Jun 15, 1995·The New England Journal of Medicine·G A ColditzF E Speizer
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·C MisseroG P Dotto
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 16, 1993·Nature·Y XiongD Beach
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·A M BambergerH M Schulte
Sep 5, 1996·Nature·R Janknecht, T Hunter
Jan 10, 1997·The Journal of Biological Chemistry·D M ProwseG P Dotto

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Citations

Aug 14, 2001·Journal of Cellular Biochemistry·S YuJ Park
Dec 22, 2007·Medical Microbiology and Immunology·Mark F Stinski, Hiroki Isomura
Sep 22, 2005·Breast Cancer Research and Treatment·A CarvajalG I Owen
Nov 11, 2008·Molecular Biology Reports·Satoru YasudaKen Iseki
May 23, 2006·Biochemical and Biophysical Research Communications·Leslie A GapterHoward L Hosick
Nov 8, 2003·Molecular and Cellular Endocrinology·Tetsuji OkazakiMasayuki Shimada
May 3, 2003·Biochemical and Biophysical Research Communications·Y Schavinsky-KhrapunskyA Torgeman
Dec 8, 2000·Steroids·R L RobkerJ S Richards
Nov 6, 2001·Molecular and Cellular Endocrinology·M Book McAlexander, L Y Yu-Lee
Jun 29, 2002·Molecular and Cellular Endocrinology·Meiyi TangLinda Tseng
Oct 25, 2011·The Journal of Biological Chemistry·Chien-Cheng ChenCarole R Mendelson
Feb 13, 2009·The Journal of Biological Chemistry·Hany Abdel-HafizKathryn B Horwitz
Oct 13, 2011·DNA and Cell Biology·Xiao ZhaoYaosheng Chen
Dec 12, 2003·Biology of Reproduction·L MittazM A Pritchard
Jul 25, 2012·Molecular and Cellular Biology·Kate BeishlineJane Azizkhan-Clifford
Mar 4, 2005·Molecular and Cellular Biology·Asmaà FritahMichèle Sabbah

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