Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3

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Homo sapiens
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PKN1, activated by phosphorylation at threonine T774, binds activated AR (androgen receptor) and promotes transcription from AR-regulated promoters. On one hand, phosphorylated PKN1 promotes the formation of a functional complex of AR with the transcriptional coactivator NCOA2 (TIF2) (Metzger et al. 2003). On the other hand, binding of phosphorylated PKN1, in complex with the activated AR, to androgen-reponsive promoters of KLK2 and KLK3 (PSA) genes, leads to PKN1-mediated histone phosphorylation. PKN1-phosphorylated histones recruit histone demethylases KDM4C (JMJD2C) and KDM1A (LSD1), and the ensuing demethylation of histones associated with the promoter regions of KLK2 and KLK3 genes increases their transcription (Metzger et al. 2005, Metzger et al. 2008).
Literature References
PubMed ID Title Journal Year
18066052 Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation

Kunowska, N, Patnaik, D, Schüle, R, Metzger, E, Wissmann, M, Potier, N, Scheidtmann, KH, Higgins, JM, Friedrichs, N, Buettner, R, Fischer, K, Yin, N

Nat. Cell Biol. 2008
16079795 LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription

Peters, AH, Schüle, R, Metzger, E, Müller, JM, Wissmann, M, Schneider, R, Buettner, R, Günther, T, Yin, N

Nature 2005
12514133 A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer

Schüle, R, Metzger, E, Müller, JM, Ferrari, S, Buettner, R

EMBO J. 2003
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