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Novel Insight into the Role of LXRa in Metabolic Regulation via DNA Binding as a Heterodimer with PPARa and as a Homodimer

Klingler, Andrea M.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1472486254

Abstract Details

2016, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
Liver X receptor a (LXRa) plays a critical role in the maintenance of energy homeostasis within a cell through tight transcriptional regulation of genes involved in metabolism of lipids, glucose, and cholesterol. Although LXRa has been established to function as a heterodimer with the retinoid X receptor a (RXRa), recent studies have determined that LXRa also interacts directly with peroxisome proliferator-activated receptor a (PPARa). However, little is known regarding the functionality of this heterodimer, if any exists at all. This study determined that a heterodimer of PPARa and LXRa is capable of binding to candidate response elements in vitro with high affinity by electrophoretic mobility shift assays and quenching of intrinsic protein fluorescence. Additionally, LXRa exhibited high affinity binding to DNA in the absence of a heterodimer partner, suggesting homodimeric interaction. Transactivation assays indicated that overexpression of PPARa and LXRa significantly increased activity of the endogenous APOA1 promoter, and overexpression of LXRa alone resulted in increased activity of all of the promoters tested, often even more so than LXRa/RXRa. These results provide new insight into the scope of metabolic regulation by LXRa, and raise important questions and considerations when targeting these proteins for treatment of metabolic disorders.
S. Dean Rider, Jr., Ph.D. (Advisor)
Steven Berberich, Ph.D. (Committee Member)
Lawrence Prochaska, Ph.D. (Committee Member)
Michael Markey, Ph.D. (Committee Member)
84 p.
Biochemistry; Molecular Biology
biochemistry; molecular biology

Recommended Citations

Citations

  • Klingler, A. M. (2016). Novel Insight into the Role of LXRa in Metabolic Regulation via DNA Binding as a Heterodimer with PPARa and as a Homodimer [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1472486254

    APA Style (7th edition)

  • Klingler, Andrea. Novel Insight into the Role of LXRa in Metabolic Regulation via DNA Binding as a Heterodimer with PPARa and as a Homodimer. 2016. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1472486254.

    MLA Style (8th edition)

  • Klingler, Andrea. "Novel Insight into the Role of LXRa in Metabolic Regulation via DNA Binding as a Heterodimer with PPARa and as a Homodimer." Master's thesis, Wright State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1472486254

    Chicago Manual of Style (17th edition)

wright1472486254
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© 2016, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.