Small carboxyl-terminal domain phosphatase 2 attenuates androgen-dependent transcription.
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.
Thompson
James
J
Institute of Biomedicine (Physiology), Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Lepikhova
Tatyana
T
Teixido-Travesa
Neus
N
Whitehead
Maria A
MA
Palvimo
Jorma J
JJ
Jänne
Olli A
OA
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000235:genetics; D054648:Protein Phosphatase 2; D012319:RNA Polymerase II / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000235:genetics
C410798:AR protein, human; D000728:Androgens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; C490060:SYCP3 protein, human; D010768:Phosphoserine; D012319:RNA Polymerase II; C413483:CTDSP1 protein, human; C108580:CTDSP2 protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D017430:Prostate-Specific Antigen