摘要
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.
摘要译文
转录因子的p53在维持体内平衡，因为它涉及细胞生长，增殖和代谢的关键作用。在努力确定新的p53的靶基因，微阵列方法被用来识别DHRS3（也称为retSDR1），为坚固的候选基因。DHRS3是短链醇脱氢酶的高度保守的成员与脂质和类维生素A代谢中的作用报道/还原酶家族。这里，我们表明，DHRS3]是通过N-末端内质网靶向信号穿梭对ER的内质网（ER）的蛋白质。对ER的一个重要功能是合成被打包成脂滴发生从ER衍生的膜，其生物合成的中性脂类。DHRS3富集在脂质液滴的联络点出芽它也定位于ER衍生的脂滴的磷脂单层。P53促进与DHRS3富集的ER一致的方式脂滴的积累。作为p53的靶基因，Dhrs3位置和潜在功能的观察提供了新的洞察p53在脂滴动力学与肿瘤细胞的代谢和肥胖影响了意想不到的作用。
Chad Deisenroth[‡][§];[1]; Yoko Itahana[‡][§];[2]; Laura Tollini[‡][§][¶]; Aiwen Jin[‡][§] and Yanping Zhang[‡][§][‖];[3]. p53-inducible DHRS3 Is an Endoplasmic Reticulum Protein Associated with Lipid Droplet Accumulation*[J]. Journal of Biological Chemistry, 2011,286(32): 28343-28356