title: E2/Estrogen receptor/sjogren syndrome-associated autoantigen relieves coactivator activator-induced G1/S arrest to promote breast tumorigenicity.
abstract: Coactivator activator (CoAA) is a dual-functional coregulator that regulates steroid receptor-mediated transcription and alternative splicing. Previously, we have shown that CoAA has tumor-suppressive potential in tumorigenic human kidney cells. Here, we uncover a molecular mechanism by which Sjogren syndrome-associated autoantigen (SSA), an estrogen receptor (ER) coactivator, induces MYC oncogene by removing repressive CoAA through E2-dependent degradation of CoAA and promotes G(1)/S transition of the cell cycle as well as anchorage-independent growth capability of breast cancer cells. We also show that E2 and ER enhance the E3 ligase activity of SSA to modulate CoAA through splicing isoform-selective ubiquitylation. We propose this as one potential molecular basis for the reduced tumor incidence in autoimmune disease patients and suggest SSA as a potential therapeutic target to treat breast cancer.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yun Kyoung
authors.initials: YK
authors.lastname: Kang
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D001940:Breast / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D059748:Proteolysis; D011960:Receptors, Estrogen / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D044763:Ubiquitin-Conjugating Enzymes / Q000276:immunology / Q000378:metabolism; D054875:Ubiquitination; D000099207:SS-A Antigen
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; D012261:Ribonucleoproteins; D044763:Ubiquitin-Conjugating Enzymes; D000099207:SS-A Antigen; C436317:RBM14 protein, human