Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand.

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Citation

Park Y, Park J, Lee Y, Lim W, Oh BC, Shin C, Kim W, Lee Y

Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand.

J Mol Med (Berl). 2011 Feb;89(2):181-91. doi: 10.1007/s00109-010-0698-y. Epub 2010 Nov 23.

PubMed ID
21104395 [ View in PubMed
]
Abstract

Mammalian MST2 kinase plays an important role in cell proliferation, survival, and apoptosis. In search of interacting proteins of MST2, we found that estrogen receptor alpha (ERalpha) co-immunoprecipitates with MST2 and its adaptor protein human Salvador (hSAV). Using reporter assays, we observed that overexpression of MST2 and hSAV leads to ligand-independent activation of ERalpha in human breast cancer MCF-7 cells, which was attenuated by the knockdown of hSAV. Furthermore, using truncated mutants of hSAV, we observed that the C terminus of hSAV is necessary and sufficient for the induction of ERalpha transactivation. The expression of hSAV and MST2 results in the phosphorylation of ERalpha at serine residues 118 and 167 and represses ERalpha expression. We then investigated the incidence of MST2 and ERalpha expression with other tumor biomarkers using commercially available tissue microarrays. Among 40 breast cancer samples analyzed, 60% (24 out of 40) expressed MST2. Nineteen among the 40 cases were MST2-positive and ERalpha-negative, implying a correlation between expressions of MST2 with loss of ERalpha in breast tumor samples. This study suggests that MST and hSAV act as novel co-regulators of ERalpha and may play an important role in breast cancer pathogenesis.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Estrogen receptorP03372Details
Serine/threonine-protein kinase 3Q13188Details