异构酶Pin1生理特性与其在肿瘤中的作用研究进展

Research progress on physiological characteristics of isomerase Pin1 and its role in tumor

摘要:

脯氨酰顺反异构酶1（peptidyl-prolyl cis-trans isomerase NIMA- interacting 1，Pin1）是细胞内磷酸化水平调节的小分子蛋白。Pin1能够特异性结合在磷酸化靶蛋白的丝氨酸/苏氨酸-脯氨酸（phosphorylated Serine/Threonine-Proline，pS/T-P）基序，将其结合的靶蛋白进行构型改变（从顺式变为反式或从反式变为顺式，Cis Trans），进而导致变构的靶蛋白结构稳定性发生改变或在细胞内的分布发生改变，并引起细胞功能改变，特别是细胞周期的异常变化、生长增殖改变等。Pin1在大多数人类恶性肿瘤中过表达，如肝癌、乳腺癌、鼻咽癌等，其通过打破癌基因和肿瘤抑制基因作用的平衡，促进肿瘤细胞的生长，因此有人称之为肿瘤发生的“催化因子”。本文综述了Pin1的生理特性与其在多种恶性肿瘤中的作用研究进展，为肿瘤分子靶向治疗提供了理论参考。

Abstract:

Peptidyl-prolyl cis-trans isomerase 1 （Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1，Pin1） is a small protein that regulates the level of phosphorylation in cells. Pin1 can specifically bind to the phosphorylated Serine/Threonine-Proline （pS/T-P） motif of phosphorylated target protein，and change the configuration of the target protein that it binds （from cis to Trans or change from trans to cis，Cis Trans）. This in turn leads to changes in the structural stability of the allosteric target protein or changes in its intracellular distribution and causes changes in cell functions，especially abnormal changes in the cell cycle，changes in growth and proliferation，and so on. Pin1 is overexpressed in most human malignant tumors，such as liver cancer，breast cancer，nasopharyngeal carcinoma，etc. It promotes the growth of tumor cells by breaking the balance between oncogenes and tumor suppressor genes. So some people call it a catalyst for tumorigenesis. This article reviews the research progress of Pin1's physiological properties and its role in various malignant tumors and provides theoretical references for tumor molecular targeted therapy.