PTB蛋白:一种调控肿瘤代谢的RNA可变剪接调节因子

Polypyrimidine tract binding protein: an alternative splicing regulatory factor which regulate tumor cell metabolism

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代谢过程的蛋白质。PTB蛋白可结合于核酸分子上富含嘧啶碱基的序列,对mRNA前体的剪接进行调控。如在部分肿瘤细胞中,PTB的表达量升高可对肿瘤代谢过程中关键的丙酮酸激酶M(pyruvate 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)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PTB蛋白的结构及其在PKM可变剪接过程中的调节机制,简要综述了PTB蛋白对肿瘤代谢的调控作用。

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 glycolysis and finally promote the tumor growth. This review mainly focus on the protein structure and the molecular mechanism of PTB to regulate the alternative splicing of PKM, which will help us to deeply understand the regulation of PTB on tumor metabolism.