Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Clin Cancer Res. 2011 Jan 1;17(1):12-8. doi: 10.1158/1078-0432.CCR-10-0752. Epub 2010 Oct 21.
Phosphorylation of the cyclin-dependent kinase inhibitor p27 by upstream mitogenic signaling pathways regulates its stability, localization, and biological function. In human cancers, loss of the antiproliferative action of p27 can arise through reduced protein levels and/or cytoplasmic mislocalization, leading to increased cell proliferation and/or cell migration, respectively. Reduced p27 expression levels and p27 mislocalization have potential prognostic and therapeutic implications in various types of human cancers. This review highlights mechanisms of functional deregulation of p27 by oncogenic signaling that provide an important molecular rationale for pathway targeting in cancer treatment.
细胞周期蛋白依赖性激酶抑制剂 p27 的磷酸化受上游有丝分裂信号通路的调节，从而调控其稳定性、定位和生物学功能。在人类癌症中，p27 的抗增殖作用丧失可能是由于蛋白水平降低和/或细胞质定位异常导致的，分别导致细胞增殖和/或细胞迁移增加。p27 表达水平降低和 p27 定位异常在各种类型的人类癌症中具有潜在的预后和治疗意义。本文重点介绍了致癌信号对 p27 功能失调的调控机制，为癌症治疗中的靶向治疗提供了重要的分子基础。
