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Abstract：
CIP/KIP and INK4 families of Cyclin-dependent kinase inhibitors (CKIs) are well-established cell cycle regulatory proteins whose canonical function is binding to Cyclin-CDK complexes and altering their function. Initial experiments showed that these proteins negatively regulate cell cycle progression and thus are tumor suppressors in the context of molecular oncology. However, expanded research into the functions of these proteins showed that most of them have non-canonical functions, both cell cycle-dependent and independent, and can even act as tumor enhancers depending on their posttranslational modifications, subcellular localization, and cell state context. This review aims to provide an overview of canonical as well as non-canonical functions of CIP/KIP and INK4 families of CKIs, discuss the potential avenues to promote their tumor suppressor functions instead of tumor enhancing ones, and how they could be utilized to design improved treatment regimens for cancer patients.
摘要：
细胞周期蛋白依赖性激酶抑制剂（CKIs）的CIP/KIP和INK4家族是公认的细胞周期调节蛋白，其典型功能是与细胞周期蛋白-CDK复合物结合并改变其功能。最初的实验表明，这些蛋白质负调节细胞周期进程，因此在分子肿瘤学背景下是肿瘤抑制因子。然而,对这些蛋白质功能的扩展研究表明，它们中的大多数具有非规范功能，细胞周期依赖性和独立性，甚至可以作为肿瘤增强子，这取决于他们的翻译后修饰，亚细胞定位，和单元格状态上下文。这篇综述旨在概述CIP/KIP和CKIs的INK4家族的规范和非规范功能，讨论促进其肿瘤抑制功能而不是肿瘤增强功能的潜在途径，以及如何利用它们为癌症患者设计改进的治疗方案。
