乙酰转移酶基因NAA10的生物学功能及其在肿瘤中的作用  

Biological Function of Acetyltransferase Gene NAA10 and Its Role in Cancer

作　　者：闵力[1] 曾妍 寿成超[1] 

机构地区：[1]北京大学临床肿瘤学院,北京肿瘤医院暨北京市肿瘤防治研究所生物化学与分子生物学研究室,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国生物化学与分子生物学报》2013年第10期902-909,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：教育部博士点基金(No.20110001110050);国家重点基础研究发展计划(973项目,No.2009CB521805)资助~~

摘　　要：N端乙酰转移酶A(N-acetyltransferase A,NatA)复合体是真核生物最主要的N端氨基酸α位乙酰转移酶,N端α位乙酰转移酶10基因(N-α-acetyltransferase 10,NAA10)编码的N端α位乙酰转移酶10蛋白(N-α-acetyltransferase 10 protein,Naa10p)是NatA的催化亚基.Naa10p具备新生蛋白质N端氨基酸α位乙酰化活性、成熟蛋白质Lys残基ε位乙酰化活性以及对部分转录因子的协同调节作用.Naa10p能够通过调节细胞周期促进细胞增殖,通过调节雷帕霉素靶蛋白(mechanistic target of rapamycin,mTOR)通路促进细胞自噬,并通过多种不同的分子信号通路抑制细胞运动能力.根据乙酰化底物的不同,Naa10p还在细胞凋亡的调控中起双重作用.Naa10p参与的生物学过程还涉及血管生成和神经发育等.Naa10p在多种癌症组织中呈过表达,但其预后意义随肿瘤不同而有较大差别.对Naa10p的生理生化研究必将使我们对细胞的生理病理学过程及其机制的了解更加深入全面.本文将从蛋白质结构、机制功能及临床意义等不同角度系统地阐述NAA10的研究现状与进展.N-acetyltransferase A （NatAl complex is the major N-αacetyltransferase in eukaryotes. Naal0p （N-α-acetyltransferase 10 protein） , the catalytic subunit of NatA, is encoded by NAAIO （N-α- acetyltransferase 10）. Naal0p catalyzes N-α-acetylation of nascent poIypeptides, lysine α-aeetylation of mature proteins, lysine autoacetylation, and acts as a transcriptional co-factor. Naal0p promotes cell proliferation by regulating cell cycle, promotes autophage by regulating roTOR （mechanistic target of rapamyein） signaling and inhibits cell motility through different molecular pathways. By acetylating different proteins, Naal0p has dual effects on cell apoptosis, and it is also involved in angiogenesis and neuron development. Naal0p is overexpressed in various types of cancer. However, its effect on cancer is context-dependent. Naal0p studies via physiological and biochemical approaches can provide a comprehensive understanding of the mechanism underlying its pathological function. This review summarizes the protein structure, molecular mechanism, cellular function and clinical significance of NaalOp, and systematically expatiates present situation and future progress in this field.

关 键 词：N端α位乙酰转移酶10基因(NAA10) 乙酰转移酶 蛋白质修饰 肿瘤 

分 类 号：Q71[生物学—分子生物学]