Breast cancer risk correlates highly with sustained estrogen receptor (ER) activities. Estrogen antagonists (e.g. anti-estrogens) and estrogen synthesis blockers (e.g. aromatase inhibitors) are frontline treatment to hinder disease progression in patients with breast cancer because most malignant breast tumors exhibit ERalpha positive expression signature. ERalpha harbors several post-translational modifications such as phosphorylation, acetylation, methylation, ubiquitination, sumoylation, palmitoylation, and others. Dysregulation of such PTMs on ERalpha enables abnormal tumor cell proliferation and promote malignancy. Although individual PTM on ERalpha is extensively deciphered, it remains relatively unclear how PTMs interact with each other to coordinate and execute 1) the recruitment of co-activators and RNA polymerase machinery to chromatin and 2) promoter clearance after transcription activation. Here, we report a novel PTM crosstalk between transcription-coupled phosphorylation and an ubiquitination-like modification on ERalpha. We also reveal its potential roles in regulating ER transcriptional activation and its future application in managing ER positive breast cancer.
Date:
2020-02
Relation:
Cancer Research. 2020 Feb;80(4, Suppl.):Meeting Abstract P6-05-13.
