Tyrosine phosphorylation regulates ERβ ubiquitination, protein turnover, and inhibition of breast cancer

Bin Yuan, Long Cheng, Kshama Gupta, Huai Chin Chiang, Harshita B. Gupta, Gangadhara R. Sareddy, Degeng Wang, Kate Lathrop, Richard Elledge, Pei Wang, Stanton McHardy, Ratna Vadlamudi, Tyler J. Curiel, Yanfen Hu, Qinong Ye, Rong Li

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Unlike estrogen receptor α (ERα) that predominantly promotes hormone-dependent breast tumor growth, ERβ exhibits antitumor effects in a variety of cancer types. We recently identified a phosphotyrosine residue in ERβ, but not ERα, that dictates ERβ transcriptional activity and antitumor function. We show here that this ER isotype-specific phosphotyrosine switch is important for regulating ERβ activity in cell proliferation, migration, and invasion. At the mechanistic level, phosphorylated ERβ, which recruits transcriptional coactivator p300, is in turn targeted by p300 for ubiquitination and proteasome-dependent protein turnover. Furthermore, ERβ-specific agonists such as S-equol enhance ERβ phosphorylation, suggesting a crosstalk between ligand- and posttranslational modification-dependent ERβ activation. Inhibition of xenograft tumor growth by S-equol is associated with reduced tumor Ki-67 expression and elevated ERβ tyrosine phosphorylation. Taken together, our data support the notion that phosphotyrosine-dependent ERβ signaling is an attractive target for anticancer treatment.

Original languageEnglish (US)
Pages (from-to)42585-42597
Number of pages13
Issue number27
StatePublished - Jul 5 2016


  • ERβ
  • antitumor activity
  • protein turnover
  • tyrosine phosphorylation
  • ubiquitination

ASJC Scopus subject areas

  • Oncology


Dive into the research topics of 'Tyrosine phosphorylation regulates ERβ ubiquitination, protein turnover, and inhibition of breast cancer'. Together they form a unique fingerprint.

Cite this