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Title: Acetylation at lysine 183 of progesterone receptor by p300 accelerates DNA binding kinetics and transactivation of direct target genes
Authors: Sze, Siu Kwan
Chung, Hwa Hwa
Tay, Alvin Shun Long
Lin, Valerie Chun Ling
Keywords: DRNTU::Science::Biological sciences::Genetics
Issue Date: 2014
Source: Chung, H. H., Sze, S. K., Tay, A. S. L., & Lin, V. C. L. (2014). Acetylation at lysine 183 of progesterone receptor by p300 accelerates DNA binding kinetics and transactivation of direct target genes. Journal of biological chemistry, 289(4), 2180-2194.
Series/Report no.: The journal of biological chemistry
Abstract: The identification of lysine acetylation of steroid hormone receptors has previously been based on the presence of consensus motif (K/R)XKK. This study reports the discovery by mass spectrometry of a novel progesterone receptor acetylation site at Lys-183 that is not in the consensus motif. In vivo acetylation and mutagenesis experiments revealed that Lys-183 is a primary site of progesterone receptor (PR) acetylation. Lys-183 acetylation is enhanced by p300 overexpression and abrogated by p300 gene silencing, suggesting that p300 is the major acetyltransferase for Lys-183 acetylation. Furthermore, p300-mediated Lys-183 acetylation is associated with heightened PR activity. Accordingly, the acetylation-mimicking mutant PRB-K183Q exhibited accelerated DNA binding kinetics and greater activity compared with the wild-type PRB on genes containing progesterone response element. In contrast, Lys-183 acetylation had no influence on PR tethering effect on the nuclear factor κ-light chain enhancer of activated B cells (NFκB). Additionally, increases of Lys-183 acetylation by p300 overexpression or inhibition of deacetylation resulted in increases of Ser-294 phosphorylation levels. In conclusion, PR acetylation at Lys-183 by p300 potentiates PR activity through accelerated binding of its direct target genes without affecting PR tethering on other transcription factors. The effect may be mediated by enhancing Ser-294 phosphorylation.
DOI: 10.1074/jbc.M113.517896
Schools: School of Biological Sciences 
Rights: © 2014 American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by The Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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