title: Phospholipid regulation of the nuclear receptor superfamily.
abstract: Nuclear receptors are ligand-activated transcription factors whose diverse biological functions are classically regulated by cholesterol-based small molecules. Over the past few decades, a growing body of evidence has demonstrated that phospholipids and other similar amphipathic molecules can also specifically bind and functionally regulate the activity of certain nuclear receptors, suggesting a critical role for these non-cholesterol-based molecules in transcriptional regulation. Phosphatidylcholines, phosphoinositides and sphingolipids are a few of the many phospholipid like molecules shown to quite specifically regulate nuclear receptors in mouse models, cell lines and in vitro. More recent evidence has also shown that certain nuclear receptors can "present" a bound phospholipid headgroup to key lipid signaling enzymes, which can then modify the phospholipid headgroup with very unique kinetic properties. Here, we review the broad array of phospholipid/nuclear receptor interactions, from the perspective of the chemical nature of the phospholipid, and the cellular abundance of the phospholipid. We also view the data in the light of well established paradigms for phospholipid mediated transcriptional regulation, as well as newer models of how phospholipids might effect transcription in the acute regulation of complex nuclear signaling pathways. Thus, this review provides novel insight into the new, non-membrane associated roles nuclear phospholipids play in regulating complex nuclear events, centered on the nuclear receptor superfamily of transcription factors.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Crowder
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, USA.
authors.forename: Corey D
authors.initials: CD
authors.lastname: Seacrist
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, USA; Department of Biochemistry, Vanderbilt University School of Medicine, USA; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University School of Medicine, USA. Electronic address: ray.blind@vanderbilt.edu.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Blind
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D008024:Ligands; D010743:Phospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors