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Thermo‐responsive Estrogen Receptor‐fusions for Spatiotemporal Control of Signaling and Gene Regulation
Author(s) -
Truong Anh T.,
Li Zhe,
Okamoto Curtis T.,
MacKay J. Andrew
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.533.102
Subject(s) - estrogen receptor , signal transduction , microbiology and biotechnology , cell , receptor , biology , transcription factor , cell signaling , estrogen , gene , chemistry , genetics , cancer , breast cancer
Many diseases are caused by aberrant cell signaling, leading to a dysregulation of proteins responsible for cell maintenance and repair. Understanding these events require a precise manipulation of the cells' machinery, but many technologies used to study signaling and transcription lack the temporal control to rapidly modulate these biologic processes. This limitation could be addressed by the introduction of elastin‐like polypeptides (ELPs) which are synthetic, thermally responsive biopolymers that self‐assemble into microdomains of ELP‐fusions within cells. Our research group recently discovered that these fusion proteins can modulate precise processes involved in cell trafficking. They are now being investigated to modulate estrogen receptor (ER) signaling and gene regulation. ER has been implicated in a number of diseases such as breast cancer and Sjögren's Syndrome and although this nuclear hormone receptor has been well studied, the lack of drug therapy and resistance, requires attention to develop a deeper understanding of the underlying mechanisms. Thus, ELP‐ERɑ fusions have been generated and successfully expressed in CHO, HeLa and 293T cell lines. They coalesce in the nucleus at physiological temperatures and rapidly solubilize at room temperature. These preliminary data indicate that these fusions retain ELPs self‐assembling properties and may control ER signaling and gene regulation. The ability to rapidly and reversibly, with spatiotemporal control and precision, may allow this fusion to serve as a powerful tool to study ER‐mediated biological processes. Support or Funding Information This funding is supported by the National Institutes of Health (NIGMS 1R01GM114839‐02) and the American College of Clinical Pharmacy Research Institute Futures Grant. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .