Research Article

鉴定Depalmitoylation酶Acyl-protein Thioesterase 1的潜在底物

卷 19, 期 5, 2019

页: [364 - 375] 页: 12

弟呕挨: 10.2174/1566524019666190325143412

价格: $65

摘要

背景:棕榈酰化和去甲基化的稳态参与各种细胞过程,其破坏引起严重的生理后果。酰基蛋白硫酯酶(APT)和棕榈酰 - 蛋白质硫酯酶(PPT)催化脱醛基化过程。人PPT1的天然突变引起神经退行性疾病,但对APT1的理解仍有待阐明。虽然小鼠中APT1的缺失证明可能是胚胎致死的,但其功能的解码严格依赖于其底物的鉴定。 目的:通过使用产生的人APT1敲除细胞系确定APT1的潜在底物。 方法:采用棕榈酰蛋白富集和质谱联用技术分析不同蛋白质。 HEK293T和APT1-KO细胞中的棕榈酰蛋白通过树脂辅助捕获(RAC)和数据独立采集(DIA)定量蛋白质组学方法提取用于数据收集。 结果:共鉴定出382种蛋白质。基因本体论分类将这些蛋白质分离成不同的生物学途径,例如内质网过程和泛素介导的蛋白水解。选择了一些潜在的基质进行验证;实际上,主要蛋白质是棕榈酰化的。重要的是,它们的棕榈酰化水平在APT1-KO细胞中明显改变。有趣的是,与WT细胞相比,APT1-KO细胞的增殖显着增加,这可以通过APT1过表达来挽救。结论:我们的研究提供了大量潜在的APT1底物,从而有助于理解其介入的分子功能。

关键词: APT1,棕榈酰化,潜在底物,质谱,数据独立获取,增殖。

[1]
Nadolski MJ, Linder ME. Protein lipidation. FEBS J 2007; 274(20): 5202-10.
[2]
Kohlschutter A, Schulz A. Towards understanding the neuronal ceroid lipofuscinoses. Brain Dev 2009; 31(7): 499-502.
[3]
Sima N, Li R, Huang W, et al. Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses. Orphanet J Rare Dis 2018; 13(1): 54.
[4]
Ozono T, Kinoshita M, Narita A, et al. Juvenile-onset neuronal ceroid lipofuscinosis (CLN1) disease with a novel deletion and duplication in the PPT1 gene. J Neurol Sci 2018; 388: 4-6.
[5]
Wisniewski KE, Gordonmajszak W, Maslinski S, et al. Altered protein patterns in brains of children with neuronal ceroid lipofuscinosis. Am J Med Genet 1992; 42(4): 568-74.
[6]
Benjannet S, Elagoz A, Wickham L, et al. Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. The pro- and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. J Biol Chem 2001; 276(14): 10879-87.
[7]
Koegl M, Zlatkine P, Ley SC, et al. Palmitoylation of multiple Src-family kinases at a homologous N-terminal motif. Biochem J 1994. 303 ( Pt 3)(3): 749-53.
[8]
Wang J, Shan C, Cao W, et al. SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface. Hum Mol Genet 2013; 22(24): 4888-900.
[9]
Butland SL, Sanders SS, Schmidt ME, et al. The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington’s disease. Hum Mol Genet 2014; 23(15): 4142-60.
[10]
Rocks O, Peyker A, Kahms M, et al. An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science 2005; 307(5716): 1746-52.
[11]
Schmick M, Kraemer A, Bastiaens PI. Ras moves to stay in place. Trends Cell Biol 2015; 25(4): 190-7.
[12]
Won SJ, Cheung See Kit M, Martin BR. Protein depalmitoylases. Crit Rev Biochem Mol Biol 2018; 53(1): 83-98.
[13]
Duncan, Gilman AG. A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J Biol Chem 1998; 273(25): 15830-7.
[14]
Kong E, Peng S, Chandra G, et al. Dynamic palmitoylation links cytosol-membrane shuttling of acyl-protein thioesterase-1 and acyl-protein thioesterase-2 with that of proto-oncogene H-Ras product and growth-associated protein-43. J Biol Chem 2013; 288(13): 9112-25.
[15]
Zeidman R, Jackson CS, Magee AI. Protein acyl thioesterases.(Review) Mol Membr Biol 2009; 26(1): 32-41.
[16]
Forrester MT, Hess DT, Thompson JW, et al. Site-specific analysis of protein S-acylation by resin-assisted capture. J Lipid Res 2011; 52(2): 393-8.
[17]
Dowal L, Yang W, Freeman MR, et al. Proteomic analysis of palmitoylated platelet proteins. Blood 2011; 118(13): e62-73.
[18]
Edmonds MJ, Geary B, Doherty MK, et al. Analysis of the brain palmitoyl-proteome using both acyl-biotin exchange and acyl-resin-assisted capture methods. Sci Rep 2017; 7(1): 3299.
[19]
Nigjeh EN, Chen R, Brand RE, et al. Quantitative Proteomics Based on Optimized Data-independent-acquisition in Plasma Analysis. J Proteome Res 2017; 16(2): 665-76.
[20]
Kim SJ, Zhang Z, Sarkar C, et al. Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice. Jof Clin Invest 2008; 118(9): 3075-86.
[21]
Sandoval D, Hill S, Ziemba A, et al. Ubiquitin-conjugating enzyme Cdc34 and ubiquitin ligase Skp1-cullin-F-box ligase (SCF) interact through multiple conformations. J Biol Chem 2015; 290(2): 1106-18.
[22]
Rojas F, Koszela J, Búa J, et al. The ubiquitin-conjugating enzyme CDC34 is essential for cytokinesis in contrast to putative subunits of a SCF complex in Trypanosoma brucei. PLoS Negl Trop Dis 2017; 11(6): e0005626.
[23]
Liu X, Zhang Y, Hu Z, et al. The catalytically inactive mutation of the ubiquitin-conjugating enzyme CDC34 affects its stability and cell proliferation. Protein J 2018; 37(2): 132-43.
[24]
Ma X, Zhao J, Yang F, et al. Ubiquitin conjugating enzyme E2 L3 promoted tumor growth of NSCLC through accelerating p27kip1 ubiquitination and degradation. Oncotarget 2017; 8(48): 84193-203.
[25]
Lewis MJ, Vyse S, Shields AM, et al. UBE2L3 polymorphism amplifies NF-κB activation and promotes plasma cell development, linking linear ubiquitination to multiple autoimmune diseases. Am J Hum Genet 2015; 96(2): 221-34.

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