前列腺癌细胞中雄激素调控核糖体蛋白和氨酰-tRNA合成酶蛋白棕榈酰化修饰  

Androgen Regulates Palmitoylation of Ribosomal Proteins and Aminoacyl-tRNA Synthetases in the Prostate Cancer-Derived LNCaP Cells

作　　者：李文卿 张伟[2] 崔芦伟 刁统祥 张大磊[3] 张亚群[3] 肖飞[1] 刘明[3] Li Wenqing;Zhang Wei;Cui Luwei;Diao Tongxiang;Zhang Dalei;Zhang Yaqun;Xiao Fei;Liu Ming(The MOH Key Laboratory of Geriatrics,Beijing Hospital,National Center of Gerontology,Beij＇ing 100730,China;Department of Pathology,Beijing Hospital,Beijing 100730,China;Department of Urology,Beijing Hospital,Beijing 100730,China)

机构地区：[1]北京医院国家老年医学中心卫生部老年医学重点实验室,北京100730 [2]北京医院病理科,北京100730 [3]北京医院泌尿外科,北京100730

出　　处：《中国细胞生物学学报》2018年第10期1699-1705,共7页Chinese Journal of Cell Biology

基　　金：十三五国家重点研发计划(批准号:2017YFC840102);中央保健局课题(批准号:W2016ZD01);首都临床特色应用研究专项(批准号:Z171100001017201)资助的课题~~

摘　　要：作者对雄激素R1881或DMSO处理的LNCaP细胞进行炔基棕榈酸代谢标记,之后利用点击化学反应形成的共价键富集棕榈酰化修饰蛋白,并对富集蛋白进行质谱定量分析,从而筛选、鉴定棕榈酰化修饰水平受雄激素诱导的蛋白。结果发现,雄激素在LNCaP细胞内促进核糖体蛋白RPL12、RPS4X和谷氨酰脯氨酰-tRNA合成酶(EPRS)棕榈酰化修饰,在细胞上清中促进甘氨酰-tRNA合成酶(GARS)棕榈酰化修饰。对RPL12、RPS4X和EPRS棕榈酰化调控机制的研究将为前列腺癌的治疗提供新的指导思路;雄激素诱导下细胞内RPL12、RPS4X和EPRS棕榈酰化修饰水平的升高可以作为相关的肿瘤标志物,细胞上清中GARS棕榈酰化修饰水平的升高对于前列腺癌的早期筛查具有重要的参考价值。Firstly, the LNCaP cells were treated with androgen （R1881） or DMSO and meanwhile the cells were metabolically labeled with Alk-C16, an alkyne analogue of palmitic acid. Secondly, the proteins conjugated with Alk-C16 were enriched in azide agarose beads based on the alkyne-azide reaction （click chemistry）. At last, the conjugated proteins were digested for mass spectrum （MS） and label-free quantitation. By comparing the protein palmitoylation levels between androgen-treated LNCaP cells and the non-treated, the proteins of which the palmitoylation levels were induced by androgen were screened and identified. The results demonstrated that androgen treatment significantly increased the palmitoylation levels of ribosomal protein RPL12, RPS4X and glutamyl- prolyl-tRNA synthetase （EPRS）. In addition, androgen treatment also increased the palmitoylation levels of glycly- tRNA synthetase （GARS） in cell supematant. The regulation of the palmitoylation for RPL12, RPS4X and EPRS might provide new directions for the therapy of prostate cancer. Moreover, the high palmitoylation level of RPL 12, RPS4X and EPRS induced by androgen may be tumor biomarkers. The high palmitoylation level of GARS induced by androgen in supernatant might be a biomarker for tumor early screening.

关 键 词：前列腺癌 雄激素 棕榈酰化 

分 类 号：R737.25[医药卫生—肿瘤]