文章：

PIN1，细胞周期和癌症

PIN1, the cell cycle and cancer

原文发布日期：2007-04-05

DOI: 10.1038/nrc2107

类型: Review Article

开放获取: 否

要点：

1. PIN1 is a member of the evolutionarily conserved peptidyl-prolyl isomerase family of proteins, which encompasses the cyclophilins, FK506-binding proteins and the parvulins.
2. PIN1 binds to and alters the conformation of phosphoproteins by catalysing the rapid cis to trans isomerization of proline amide bonds contained within the target proteins.
3. The isomerization of proteins by PIN1 results in an alteration of protein structure and/or function, which is often coupled to a change in protein stabilization.
4. PIN1 was originally identified as a cell cycle protein (mitotic). Subsequently, many cell-cycle regulatory proteins (G1/S, M and checkpoint) were identified as PIN1 binding partners. Given its ability to regulate these important proteins, PIN1 is suggested to act a molecular 'timer' of the cell cycle.
5. PIN1 is overexpressed in some human cancers in correlation with cyclin D1 and β-catenin overexpression. Such correlations have led to the idea that PIN1 might be tumour promoting.
6. The loss of PIN1 also promotes the stabilization of two important oncogenes, MYC and cyclin E. The germline deletion of Pin1 promotes rapid genomic instability in mouse embryo fibroblasts in a p53-dependent manner that encourages more aggressive Ras-induced transformation of these PIN1-null cells. Therefore, it has been suggested that PIN1 might act as a tumour suppressor.
7. The contradictory experimental observations regarding the function of PIN1 in cancer remain enigmatic, but raise the possibility that PIN1 can either function as a tumour promoter or conditional tumour suppressor.

要点翻译：

1. PIN1是进化上高度保守的肽基脯氨酰异构酶蛋白家族的成员，该家族包括亲环蛋白、FK506结合蛋白以及细小蛋白。
2. PIN1通过催化靶蛋白中脯酰胺键的快速顺反异构化，结合并改变磷酸化蛋白质的构象。
3. PIN1介导的蛋白质异构化会导致蛋白质结构和/或功能的改变，这种改变常与蛋白质稳定性的变化相关联。
4. PIN1最初被鉴定为一种细胞周期蛋白（有丝分裂期）。随后，许多细胞周期调控蛋白（G1/S期、M期及检验点）被确认为PIN1的结合伴侣。鉴于其调控这些关键蛋白的能力，PIN1被认为在细胞周期中扮演分子"计时器"的角色。
5. 在某些人类癌症中，PIN1与细胞周期蛋白D1和β-连环蛋白共同过表达。这种相关性使人们认为PIN1可能具有促肿瘤作用。
6. 而PIN1的缺失也会促进两种重要癌基因MYC和细胞周期蛋白E的稳定。在小鼠胚胎成纤维细胞中，Pin1的种系缺失会以p53依赖性方式加速基因组不稳定性，从而促使这些PIN1缺失细胞发生更侵袭性的Ras诱导转化。因此，也有研究认为PIN1可能发挥肿瘤抑制因子功能。
7. 关于PIN1在癌症中功能的这些矛盾实验观察仍存争议，但提示了PIN1可能兼具促癌因子和条件性抑癌因子的双重潜能。

英文摘要：

PIN1 is a peptidyl-prolyl isomerase that can alter the conformation of phosphoproteins and so affect protein function and/or stability. PIN1 regulates a number of proteins important for cell-cycle progression and, based on gain- and loss-of-function studies, is presumed to operate as a molecular timer of this important process. Therefore, it seems logical that alterations in the level of PIN1 can influence hyperproliferative diseases such as cancer. However, the precise role of PIN1 in cancer remains controversial.

摘要翻译： 

PIN1是一种肽基脯氨酰异构酶，能够改变磷酸化蛋白的构象，从而影响其功能和/或稳定性。PIN1调控多个与细胞周期进程相关的重要蛋白，基于功能获得与缺失研究，被认为在该过程中充当分子计时器。因此，PIN1水平的变化似乎理应会影响癌症等过度增殖性疾病。然而，PIN1在癌症中的确切作用仍存在争议。

原文链接：

PIN1, the cell cycle and cancer