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适时的细胞周期调控,是通过丝氨酸-苏氨酸激酶家族中称为细胞周期依赖性激酶(CDKs)成员的序贯活化来实现的。细胞周期蛋白依赖性激酶抑制剂(CDKIs)参与了CDK的调控过程,在细胞周期的不同时相,CDKIs确保CDK正确的激活时间。p27~(KIPI)是CDKIs的重要成员之一,无论是在正常细胞还是在肿瘤细胞,p27~(KIPI)的调控作用与其在细胞内的定位有关,p27~(KIPI)位于核内和位于胞浆时能产生截然相反的生物学作用。p27~(KIPI)蛋白的调控主要依靠蛋白酶降解,在人类多种肿瘤中存在p27~(KIPI)的表达下调,其表达下调与肿瘤患者预后不良有关。但p27~(KIPI)基因有别于通常所指的肿瘤抑制基因,其突变在肿瘤中十分罕见。p27~(KIPI)的肿瘤抑制功能是通过抑制cyclin/CDK复合物来实现的,其致瘤功能不依赖于cyclin/CDK,而与p27~(KIPI)定位于细胞浆有关。本文就p27~(KIPI)蛋白的基本特征和最新研究进展进行综述,分别阐述其抑瘤和致瘤功能。
Proper cell-cycle regulation is achieved through sequential activation of members of the serine-threonine kinase family called cell cycle-dependent kinases (CDKs). Cyclin-dependent kinase inhibitors (CDKIs) are involved in the regulation of CDK and CDKIs ensure the correct CDK activation time at different phases of the cell cycle. P27 ~ (KIPI) is one of the important members of CDKIs. The regulation of p27 ~ (KIPI) is related to its intracellular localization both in normal cells and in tumor cells. P27 ~ (KIPI) Syrup can produce the opposite biological effects. The regulation of p27KIPI mainly depends on the protease degradation. The expression of p27KIPI is down-regulated in many human tumors. The down-regulation of p27 KIPI is associated with the poor prognosis of cancer patients. However, the p27KIPI gene differs from the commonly used tumor suppressor genes in that mutations are rare in tumors. The tumor suppressor function of p27 KIPI is through the inhibition of cyclin / CDK complex. The tumorigenic function is not dependent on cyclin / CDK but is related to the localization of p27 KIPI in the cytoplasm. This review summarizes the basic features of p27KIPI protein and the latest research progress, and expounds its antitumor and tumorigenicity respectively.