School of Life Science, Southwest University. No.1, Tiansheng Road, Beibei District, 400715, Chongqing, China.
Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University. No.183, Xinqiao Main Street, Shapingba District, 400037, Chongqing, China.
Cell Death Dis. 2018 Aug 29;9(9):883. doi: 10.1038/s41419-018-0844-y.
Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.
Pin1 是唯一已知的能够特异性识别并使磷酸化丝氨酸/苏氨酸-脯氨酸(pSer/Thr-Pro)基序发生顺反异构的肽基脯氨酰顺反异构酶(PPIase)。Pin1 介导的结构转化可在后翻译水平上调节多种蛋白质的生物功能。Pin1 参与许多细胞过程,其异常会导致退行性和肿瘤性疾病。Pin1 在大多数癌症中高度表达,其缺失可显著抑制癌症进展。根据 Hanahan D 和 Weinberg RA 的开创性总结,癌症的标志包括十个生物学特征。多项研究表明,Pin1 通过促进多种致癌途径,有助于癌症的这些异常行为。本综述总结了 Pin1 在不同癌症能力中的详细机制,以及表现出抗癌活性的某些 Pin1 靶向小分子化合物,期望通过靶向 Pin1 促进抗癌疗法。