蛋白一种调控肿瘤代谢的RNA可变剪接调节因子.pdfVIP

生命的化学, 2014, 34(3): 369-375冯浩, 等. PTB蛋白：一种调控肿瘤代谢的 RNA可变剪接调节因子doi: 10.13488/j.smhx 369 · 综述 PTB蛋白：一种调控肿瘤代谢的RNA可变剪接调节因子 冯浩，沙保勇，高兴春，景晓红* (西安医学院基础医学研究所，西安 710021) 摘要：多聚嘧啶区结合蛋白(polypyrimidine tract binding protein, PTB或hnRNP I)是一种在细胞内部参与 mRNA PTB mRNA 代谢过程的蛋白质。 蛋白可结合于核酸分子上富含嘧啶碱基的序列，对 前体的剪接 PTB M(pyru- 进行调控。如在部分肿瘤细胞中， 的表达量升高可对肿瘤代谢过程中关键的丙酮酸激酶 vate kinase M, PKM)基因的表达进行调控，通过抑制PKM基因的可变剪接的方式上调PKM2(pyruvate kinase M2, PKM2) PTB 的表达，进而强化肿瘤细胞的有氧糖酵解过程并促进肿瘤的发展。本文结合 蛋 PKM PTB 白的结构及其在 可变剪接过程中的调节机制，简要综述了 蛋白对肿瘤代谢的调控作用。 关键词：多聚嘧啶区结合蛋白；可变剪接；丙酮酸激酶M Polypyrimidine tract binding protein: an alternative splicing regulatory factor which regulate tumor cell metabolism FENG Hao, SHA Baoyong, GAO Xingchun, JING Xiaohong* (Institute of Basic Medical Science, Xi’an Medical University, Xi’an 710021, China) Abstract: Polypyrimidine tract binding protein (PTB) is known as an RNA-binding protein involved in mul- tiple aspects of messenger RNA (mRNA) metabolism. Accumulated evidence has suggested that PTB protein can bind to the pyrimidine-rich nucleic acid sequences to change the secondary structure of mRNA precursor, and regulate the activities of RNA splicing site and branch site to control mRNA precursor splicing. In many tumor cells, PTB has been found to be up-regulated, and the increase of PTB can enhance the pyruvate kinase M2 (PKM2) expression via suppression of alternative splicing of PKM, then strengthen aerobic glycoly