Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106919
Title: Protein arginine methyltransferase 6 enhances ligand-dependent and -independent activity of estrogen receptor α via distinct mechanisms
Authors: Sun, Yang
Chung, Hwa Hwa
Woo, Amanda Rui En
Lin, Valerie C.-L.
Keywords: DRNTU::Science::Biological sciences::Molecular biology
Issue Date: 2014
Source: Sun, Y., Chung, H. H., Woo, A. R. E., & Lin, V. C.-L. (2014). Protein arginine methyltransferase 6 enhances ligand-dependent and -independent activity of estrogen receptor α via distinct mechanisms. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1843(9), 2067-2078.
Series/Report no.: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Abstract: Recent studies reported that protein arginine methyltransferase 6 (PRMT6) enhances estrogen-induced activity of estrogen receptor α (ERα) and dysfunction of PRMT6 is associated with overall better survival for ERα-positive breast cancer patients. However, it is unclear how PRMT6 promotes ERα activity. Here we report that PRMT6 specifically interacts with ERα at its ligand-binding domain. PRMT6 also methylates ERα both in vitro and in vivo. In addition to enhancing estrogen-induced ERα activity, PRMT6 over-expression up-regulates estrogen-independent activity of ERα and PRMT6 gene silencing in MCF7 cells inhibits ligand-independent ERα activation. More interestingly, the effect of PRMT6 on the ligand-independent ERα activity does not require its methyltransferase activity. Instead, PRMT6 competes with Hsp90 for ERα binding: PRMT6 and Hsp90 bindings to ERα are mutually exclusive and PRMT6 over-expression reduces ERα interaction with Hsp90. In conclusion, PRMT6 requires its methyltransferase activity to enhance ERα's ligand-induced activity, but its effect on ligand-independent activity is likely mediated through competing with Hsp90 for binding to the C-terminal domain of ERα. PRMT6-ERα interaction would prevent ERα-Hsp90 association. Since Hsp90 and associated chaperones serve to maintain ERα conformation for ligand-binding yet functionally inactive, inhibition of ERα-Hsp90 interaction would relieve ERα from the constraint of chaperone complex.
URI: https://hdl.handle.net/10356/106919
http://hdl.handle.net/10220/25191
ISSN: 0167-4889
DOI: 10.1016/j.bbamcr.2014.04.008
Rights: © 2014 Elsevier B.V. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Elsevier B.V. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bbamcr.2014.04.008].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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