鉴定出鼠 CGI-58 的一种新型剪接异构体。
Identification of a novel splicing isoform of murine CGI-58.
机构信息
Department of Pediatrics, University of Kentucky, Lexington, KY 40536-0509, USA.
出版信息
FEBS Lett. 2010 Mar 5;584(5):903-10. doi: 10.1016/j.febslet.2009.12.058. Epub 2010 Jan 18.
Abstract
The comparative gene identification-58 (CGI-58) gene, mutations of which are linked to Chanarin-Dorfman syndrome, encodes a protein of the alpha/beta hydrolase domain subfamily. We report here a new alternative splicing isoform of the murine CGI-58 gene, termed mCGI-58S. Sequence comparison indicates the lack of second and third exons in this cDNA variant. While the full-length protein displayed perilipin-dependent localization to lipid droplets, mCGI-58S showed a predominant cytoplasmic staining when expressed in cells. mCGI-58S was incapable of activating adipose triglyceride lipase but retained the capacity to acylate lysophosphatidic acid. Overexpression of mCGI-58S failed to promote lipid droplet turnover and loss of intracellular triacylglycerols. These results suggest that this splicing event may be involved in the regulation of lipid homeostasis.
摘要
比较基因鉴定-58（CGI-58）基因的突变与 Chanarin-Dorfman 综合征有关，该基因编码一种属于α/β水解酶结构域亚家族的蛋白质。我们在此报道了一种新的鼠 CGI-58 基因的选择性剪接异构体，称为 mCGI-58S。序列比较表明，该 cDNA 变体缺少第二和第三个外显子。全长蛋白显示出依赖于 perilipin 的脂滴定位，而 mCGI-58S 在细胞中表达时则主要呈现细胞质染色。mCGI-58S 不能激活脂肪甘油三酯脂肪酶，但保留酰化溶血磷脂酸的能力。mCGI-58S 的过表达未能促进脂滴周转和细胞内三酰基甘油的损失。这些结果表明，这种剪接事件可能参与了脂质稳态的调节。
相似文献
1
Identification of a novel splicing isoform of murine CGI-58.
FEBS Lett. 2010 Mar 5;584(5):903-10. doi: 10.1016/j.febslet.2009.12.058. Epub 2010 Jan 18.
2
The N-terminal region of comparative gene identification-58 (CGI-58) is important for lipid droplet binding and activation of adipose triglyceride lipase.
J Biol Chem. 2010 Apr 16;285(16):12289-98. doi: 10.1074/jbc.M109.064469. Epub 2010 Feb 17.
3
Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.
Cell Metab. 2006 May;3(5):309-19. doi: 10.1016/j.cmet.2006.03.005.
4
Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond.
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Oct;1862(10 Pt B):1233-1241. doi: 10.1016/j.bbalip.2017.07.016. Epub 2017 Aug 4.
5
Alternative splicing and developmental and hormonal regulation of porcine comparative gene identification-58 (CGI-58) mRNA.
J Anim Sci. 2012 Dec;90(12):4346-54. doi: 10.2527/jas.2012-5151. Epub 2012 Jul 24.
6
Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58).
J Biol Chem. 2010 Mar 5;285(10):7300-11. doi: 10.1074/jbc.M109.081877. Epub 2009 Dec 18.
7
CGI-58/ABHD5 is phosphorylated on Ser239 by protein kinase A: control of subcellular localization.
J Lipid Res. 2015 Jan;56(1):109-21. doi: 10.1194/jlr.M055004. Epub 2014 Nov 24.
8
CGI-58 interacts with perilipin and is localized to lipid droplets. Possible involvement of CGI-58 mislocalization in Chanarin-Dorfman syndrome.
J Biol Chem. 2004 Jul 16;279(29):30490-7. doi: 10.1074/jbc.M403920200. Epub 2004 May 10.
9
CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation.
J Lipid Res. 2007 May;48(5):1078-89. doi: 10.1194/jlr.M600493-JLR200. Epub 2007 Feb 17.
10
Comparative gene identification 58/α/β hydrolase domain 5 lacks lysophosphatidic acid acyltransferase activity.
J Lipid Res. 2014 Aug;55(8):1750-61. doi: 10.1194/jlr.M051151. Epub 2014 May 30.
引用本文的文献
1
Hints on ATGL implications in cancer: beyond bioenergetic clues.
Cell Death Dis. 2018 Feb 22;9(3):316. doi: 10.1038/s41419-018-0345-z.
2
Adipose Triglyceride Lipase Regulation: An Overview.
Curr Protein Pept Sci. 2018;19(2):221-233. doi: 10.2174/1389203718666170918160110.
3
Comparative gene identification-58 (CGI-58) promotes autophagy as a putative lysophosphatidylglycerol acyltransferase.
J Biol Chem. 2014 Nov 21;289(47):33044-53. doi: 10.1074/jbc.M114.573857. Epub 2014 Oct 14.
4
Differential expressions of G0/G1 switch gene 2 and comparative gene identification-58 are associated with fat content in bovine muscle.
Lipids. 2014 Jan;49(1):1-14. doi: 10.1007/s11745-013-3866-3. Epub 2013 Nov 24.
5
Biochemistry and pathophysiology of intravascular and intracellular lipolysis.
Genes Dev. 2013 Mar 1;27(5):459-84. doi: 10.1101/gad.209296.112.
6
Distinct roles for alpha-beta hydrolase domain 5 (ABHD5/CGI-58) and adipose triglyceride lipase (ATGL/PNPLA2) in lipid metabolism and signaling.
Adipocyte. 2012;1(3):123-131. doi: 10.4161/adip.20035.
7
Recent insights into the structure and function of comparative gene identification-58.
Curr Opin Lipidol. 2011 Jun;22(3):149-58. doi: 10.1097/MOL.0b013e328346230e.
8
Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores.
Prog Lipid Res. 2011 Jan;50(1):14-27. doi: 10.1016/j.plipres.2010.10.004. Epub 2010 Nov 16.
本文引用的文献
1
Coatomer-dependent protein delivery to lipid droplets.
J Cell Sci. 2009 Jun 1;122(Pt 11):1834-41. doi: 10.1242/jcs.045849.
2
Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes.
J Biol Chem. 2009 Jul 3;284(27):18282-91. doi: 10.1074/jbc.M109.008631. Epub 2009 May 11.
3
Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5.
Am J Physiol Endocrinol Metab. 2009 Aug;297(2):E289-96. doi: 10.1152/ajpendo.00099.2009. Epub 2009 Apr 28.
4
Chanarin-Dorfman syndrome: deficiency in CGI-58, a lipid droplet-bound coactivator of lipase.
Biochim Biophys Acta. 2009 Jun;1791(6):519-23. doi: 10.1016/j.bbalip.2008.10.012. Epub 2008 Nov 12.
5
Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores.
J Lipid Res. 2009 Jan;50(1):3-21. doi: 10.1194/jlr.R800031-JLR200. Epub 2008 Oct 23.
6
CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid.
J Biol Chem. 2008 Sep 5;283(36):24525-33. doi: 10.1074/jbc.M801783200. Epub 2008 Jul 7.
7
The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding.
J Biol Chem. 2008 Jun 20;283(25):17211-20. doi: 10.1074/jbc.M710566200. Epub 2008 Apr 29.
8
YLR099C (ICT1) encodes a soluble Acyl-CoA-dependent lysophosphatidic acid acyltransferase responsible for enhanced phospholipid synthesis on organic solvent stress in Saccharomyces cerevisiae.
J Biol Chem. 2008 Apr 11;283(15):9768-75. doi: 10.1074/jbc.M708418200. Epub 2008 Feb 4.
9
Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.
Cell Metab. 2006 May;3(5):309-19. doi: 10.1016/j.cmet.2006.03.005.
10
Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase.
Science. 2004 Nov 19;306(5700):1383-6. doi: 10.1126/science.1100747.
Zotero 插件