Small carboxyl-terminal domain phosphatase 2 attenuates androgen-dependent transcription

被引:29
作者
Thompson, James
Lepikhova, Tatyana
Teixido-Travesa, Neus
Whitehead, Maria A.
Palvimo, Jorma J.
Janne, Olli A.
机构
[1] Univ Helsinki, Inst Biomed Physiol, Biomedicum, FIN-00014 Helsinki, Finland
[2] Univ Kuopio, Dept Med Biochem, FIN-70211 Kuopio, Finland
[3] Univ Helsinki, Cent Hosp, Dept Clin Chem, Helsinki, Finland
关键词
androgen receptor; glucocorticoid receptor; HYA22; RNA polymerase II; SCP1; SCP3;
D O I
10.1038/sj.emboj.7601161
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small carboxyl-terminal domain ( CTD) phosphatase 2 ( SCP2) was identified and verified as a protein that interacts with the androgen receptor ( AR). Ectopic expression of SCP2 or two other family members, SCP1 and SCP3, attenuated AR transcriptional activity in LNCaP cells and were recruited in an androgen- and AR-dependent fashion onto the prostate-specific antigen ( PSA) promoter. Silencing SCP2 and SCP1 by short hairpin RNAs increased androgen- dependent transcription of the PSA gene and augmented AR loading onto the PSA promoter and enhancer. SCP2 also attenuated glucocorticoid receptor ( GR) function, and its silencing increased dexamethasone-mediated PSA mRNA accumulation and GR loading onto the PSA enhancer in LNCaP 1F5 cells. SCP2 silencing was accompanied by augmented recruitment and earlier cycling of RNA polymerase II on the promoter. Ser 5 phosphorylation of the RNA polymerase II CTD, a process necessary for initiation of transcription elongation, occurred significantly earlier in SCP2-silenced than parental LNCaP cells. Collectively, our results suggest that SCP2 is involved in promoter clearance during steroid-activated transcription.
引用
收藏
页码:2757 / 2767
页数:11
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