TY - JOUR
T1 - Tyrosine phosphorylation regulates ERβ ubiquitination, protein turnover, and inhibition of breast cancer
AU - Yuan, Bin
AU - Cheng, Long
AU - Gupta, Khama
AU - Chiang, Hoai-Chin
AU - Gupta, Harshita
AU - Sareddy, Gangadhara
AU - Wang, Degeng
AU - Lathrop, Kate
AU - Allege, Richard
AU - Wang, Pei
AU - McHardy, Stanton
AU - Vadlamudi, Ratna
AU - Curiel, Tyler J.
AU - Hu, Yanfen
AU - Ye, Qinong
AU - Li, Rong
PY - 2016/7/5
Y1 - 2016/7/5
N2 - 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 not
AB - 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 not
M3 - Article
SP - 42585
EP - 42597
JO - Oncotarget
JF - Oncotarget
ER -