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Of the SUMO-specific proteases (SENP)-1, -2, -3, -5, and -6, only SENP1 and SENP2 are efficient in cleaving AR-SUMO-1 conjugates in intact cells and in vitro. Both SENP1 and -2 are nuclear and found at sites proximal to AR. Their expression promotes AR-dependent transcription, but in a promoter-selective fashion. SENP1 and -2 stimulated the activity of holo-AR on compound androgen response element-containing promoters. The effects of SENP1 and -2 on AR-dependent transcription were dependent on catalytic activity and required intact SUMO acceptor sites in AR, indicating that their coactivating effects are mainly due to their direct isopeptidase activity on holo-AR. In prostate cancer cells, ectopic expression of SENP1, but not that of SENP2, increased the transcription activity of endogenous AR. Silencing of SENP1 attenuated the expression of several AR target genes and blunted androgen-stimulated growth of LNCaP cells. Our results indicate that SENP1 reverses the ligand-induced SUMOylation of AR and helps fine tune the cellular responses to androgens in a target promoter-selective manner.<\/jats:p>","DOI":"10.1210\/me.2008-0219","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T01:24:59Z","timestamp":1230686699000},"page":"292-307","source":"Crossref","is-referenced-by-count":93,"title":["SUMO-Specific Protease 1 (SENP1) Reverses the Hormone-Augmented SUMOylation of Androgen Receptor and Modulates Gene Responses in Prostate Cancer Cells"],"prefix":"10.1210","volume":"23","author":[{"given":"Sanna","family":"Kaikkonen","sequence":"first","affiliation":[{"name":"Institute of Biomedicine\/Medical Biochemistry (S.K., T.J., M.M.R., H.M., J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Ja\u0308a\u0308skela\u0308inen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine\/Medical Biochemistry (S.K., T.J., M.M.R., H.M., J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Karvonen","sequence":"additional","affiliation":[{"name":"Biomedicum Helsinki (U.K.), Institute of Biomedicine, University of Helsinki, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia M.","family":"Rytinki","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine\/Medical Biochemistry (S.K., T.J., M.M.R., H.M., J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harri","family":"Makkonen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine\/Medical Biochemistry (S.K., T.J., M.M.R., H.M., J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gioeli","sequence":"additional","affiliation":[{"name":"Departments of Microbiology (D.G.), Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce M.","family":"Paschal","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics (B.M.P.), University of Virginia Health System, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorma J.","family":"Palvimo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine\/Medical Biochemistry (S.K., T.J., M.M.R., H.M., J.J.P.), University of Kuopio, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614243127500_R1","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1021\/cr020456u","article-title":"Chemistry and structural biology of androgen 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