title: p53-Inducible DHRS3 is an endoplasmic reticulum protein associated with lipid droplet accumulation.
abstract: The transcription factor p53 plays a critical role in maintaining homeostasis as it relates to cellular growth, proliferation, and metabolism. In an effort to identify novel p53 target genes, a microarray approach was utilized to identify DHRS3 (also known as retSDR1) as a robust candidate gene. DHRS3 is a highly conserved member of the short chain alcohol dehydrogenase/reductase superfamily with a reported role in lipid and retinoid metabolism. Here, we demonstrate that DHRS3 is an endoplasmic reticulum (ER) protein that is shuttled to the ER via an N-terminal endoplasmic reticulum targeting signal. One important function of the ER is synthesis of neutral lipids that are packaged into lipid droplets whose biogenesis occurs from ER-derived membranes. DHRS3 is enriched at focal points of lipid droplet budding where it also localizes to the phospholipid monolayer of ER-derived lipid droplets. p53 promotes lipid droplet accumulation in a manner consistent with DHRS3 enrichment in the ER. As a p53 target gene, the observations of Dhrs3 location and potential function provide novel insight into an unexpected role for p53 in lipid droplet dynamics with implications in cancer cell metabolism and obesity.
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of North Carolina at Chapel Hill,Chapel Hill, North Carolina 27599, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Deisenroth
authors.forename: Yoko
authors.initials: Y
authors.lastname: Itahana
authors.forename: Laura
authors.initials: L
authors.lastname: Tollini
authors.forename: Aiwen
authors.initials: A
authors.lastname: Jin
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D041721:3T3-L1 Cells; D000429:Alcohol Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology*; D050356:Lipid Metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000429:Alcohol Oxidoreductases; C586097:DHRS3 protein, mouse; C084155:alcohol dehydrogenase (NAD(P)+)