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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.

SUBMITTER: Kang YK

PROVIDER: S-EPMC3993604 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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E2/Estrogen receptor/sjogren syndrome-associated autoantigen relieves coactivator activator-induced G1/S arrest to promote breast tumorigenicity.

Kang Yun Kyoung YK Jung Sung Yun SY Qin Jun J Li Chao C Tsai Sophia Y SY Tsai Ming-Jer MJ O'Malley Bert W BW

Molecular and cellular biology 20140224 9

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 ...[more]

PMID: 24567374

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Dataset Information

E2/Estrogen receptor/sjogren syndrome-associated autoantigen relieves coactivator activator-induced G1/S arrest to promote breast tumorigenicity.

Publications

E2/Estrogen receptor/sjogren syndrome-associated autoantigen relieves coactivator activator-induced G1/S arrest to promote breast tumorigenicity.

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