title: Loss of SUMOylation on ATF3 inhibits proliferation of prostate cancer cells by modulating CCND1/2 activity.
abstract: SUMOylation plays an important role in regulating a wide range of cellular processes. Previously, we showed that ATF3, a stress response mediator, can be SUMOylated and lysine 42 is the major SUMO site. However, the significance of ATF3 SUMOylation in biological processes is still poorly understood. In the present study, we investigated the role of ATF3 SUMOylation on CCND activity and cellular proliferation in human prostate cancer cells. First, we showed that ATF3 can be SUMOylated endogenously in the overexpression system, and lysine 42 is the major SUMO site. Unlike normal prostate tissue and androgen-responsive LNCaP cancer cells, androgen-independent PC3 and DU145 cancer cells did not express ATF3 endogenously. Overexpression of ATF3 increased CCND1/2 expression in PC3 and DU145 cancer cells. Interestingly, we observed that SUMOylation is essential for ATF3-mediated CCND1/2 activation. Finally, we observed that SUMOylation plays a functional role in ATF3-mediated cellular proliferation in PC3 and DU145 cells. Taken together, our results demonstrate that SUMO modification of ATF3 influences CCND1/2 activity and cellular proliferation of prostate cancer PC3 and DU145 cells and explains at least in part how ATF3 functions to regulate cancer development.
authors.affiliation: Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA. yang_w@mercer.edu.
authors.forename: Chiung-Min
authors.initials: CM
authors.lastname: Wang
authors.forename: Wei-Hsiung
authors.initials: WH
authors.lastname: Yang
mesh_terms: D051700:Activating Transcription Factor 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000728:Androgens / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008297:Male; D016297:Mutagenesis, Site-Directed; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation; D014162:Transfection
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D000728:Androgens; C530104:CCND1 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D019938:Cyclin D1; D008239:Lysine