title: Histone H2B ubiquitin ligases RNF20 and RNF40 in androgen signaling and prostate cancer cell growth.
abstract: Since data-mining from the Oncomine database revealed that expression of histone H2B K120 monoubiquitin (H2Bub1) ligase RNF20 is decreased in metastatic prostate cancer, we elucidated the effect of RNF20 and its homolog RNF40 on androgen receptor (AR)-dependent transcription and prostate cancer cell growth. Both RNF20 and RNF40 were able to functionally and physically interact with the AR and modulate its transcriptional activity in intact cells. Chromatin immunoprecipitation analyses showed that the androgen induction of FKBP51 and PSA in LNCaP prostate cancer cells is accompanied with a dynamic increase in the H2Bub1 within the transcribed regions of these loci. Interestingly, depletion of RNF20 or RNF40 strongly retarded the growth of LNCaP cells, which was however unlikely to be due to altered androgen signaling, but due to decreased expression of several cell cycle promoters. Collectively, our results suggest that RNF20 and RNF40, either via ubiquitylation of H2B or other targets, are coupled to the proliferation of prostate cancer cells.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Jääskeläinen
authors.forename: Harri
authors.initials: H
authors.lastname: Makkonen
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Kim
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008745:Methylation; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000099159:Tacrolimus Binding Protein 5
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D008156:Luciferases; D017430:Prostate-Specific Antigen; D011944:Receptors, Androgen; D022021:Tacrolimus Binding Proteins; D013739:Testosterone; D044767:Ubiquitin-Protein Ligases; D000099159:Tacrolimus Binding Protein 5; C506646:RNF20 protein, human; C413363:RNF40 protein, human