蛋白磷酸酶1结构和生物学功能及其与肿瘤发生发展关系的研究进展

doi:10.13481/j.1671-587X.20250329

摘要/Abstract

摘要：

蛋白磷酸酶1（PP1）是一种生物体内广泛表达且高度保守的丝氨酸-苏氨酸磷酸酶，通过催化多种蛋白去磷酸化调控细胞信号传导通路，进而影响细胞增殖、凋亡、迁移和转录等生物学过程。在体内，PP1不以自由的催化亚基存在，而是至少与一个PP1调节蛋白（PIP）结合，形成不同的PP1全酶。PP1的催化亚基与特异性调节蛋白之间的相互作用是PP1功能的核心。正常情况下，PP1在体内稳定地发挥去磷酸化作用，但在肿瘤中PP1的功能被异常调控，导致PP1活性升高或降低。PP1对肿瘤的发生发展具有双重影响，在部分肿瘤中发挥抑制作用，部分肿瘤中起促进作用。现基于国内外对PP1的研究成果，针对PP1的结构、生物功能及其各亚基对乳腺癌、肺癌、卵巢癌、胰腺癌（PAAD）、肝癌，子宫内膜癌、食管癌（EC）、结直肠癌和胶质母细胞瘤（GBM）等不同肿瘤发生发展的影响进行综述，为开发靶向PP1全酶的高效绿色抗癌药物和治疗方法提供参考。

关键词: 蛋白磷酸酶1, 丝氨酸-苏氨酸磷酸酶, 蛋白磷酸酶1调节蛋白, 生物学功能, 去磷酸化

Abstract:

Protein phosphatase 1 （PP1） is a widely expressed and highly conserved serine/threonine phosphatase in organisms. It regulates cellular signaling pathways by catalyzing the dephosphorylation of various proteins， thereby influencing biological processes such as cell proliferation， apoptosis， migration， and transcription. In vivo， PP1 does not exist as a free catalytic subunit but instead forms distinct PP1 holoenzymes by binding with at least one PP1-interacting protein （PIP）. The interaction between PP1’s catalytic subunit and its specific regulatory proteins is central to PP1’s function. Under normal conditions， PP1 stably performs its dephosphorylation role in vivo； however， in tumors， PP1 function is aberrantly regulated， leading to either increased or decreased PP1 activity. PP1 exerts a dual influence on tumorigenesis and progression， acting as a suppressor in some cancers while promoting oncogenesis in others. Based on domestic and international research findings on PP1， this review summarizes the structure and biological functions of PP1， as well as the impact of its various subunits on the development and progression of different cancers， including breast cancer， lung cancer， ovarian cancer， pancreatic adenocarcinoma （PAAD）， liver cancer， endometrial cancer， esophageal cancer （EC）， colorectal cancer， and glioblastoma （GBM）. This review aims to provide the insights for developing highly efficient and environmentally friendly anticancer drugs and therapeutic approaches targeting PP1 holoenzymes.

Key words: Protein phosphatase 1, Serine-threonine phosphatase, Protein phosphatase 1 regulatory proteins, Biological function, Dephosphorylation

中图分类号:

R730.2

郭文秀,张慧灵,孟峻. 蛋白磷酸酶1结构和生物学功能及其与肿瘤发生发展关系的研究进展[J]. 吉林大学学报(医学版), 2025, 51(3): 822-830.

Wengxiu GUO,Huiling ZHANG,Jun MENG. Research progress in structure and biological function of protein phosphatase 1 and its relationship with occurence and development of tumor[J]. Journal of Jilin University(Medicine Edition), 2025, 51(3): 822-830.

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