Molecular Carcinogenesis Group, Laboratory of Histology-Embryology, Medical School, University of Athens, Greece.
Mol Cancer Res. 2009 Dec;7(12):1902-19. doi: 10.1158/1541-7786.MCR-09-0317. Epub 2009 Nov 24.
p57(KIP2) is an imprinted gene located at the chromosomal locus 11p15.5. It is a cyclin-dependent kinase inhibitor belonging to the CIP/KIP family, which includes additionally p21(CIP1/WAF1) and p27(KIP1). It is the least studied CIP/KIP member and has a unique role in embryogenesis. p57(KIP2) regulates the cell cycle, although novel functions have been attributed to this protein including cytoskeletal organization. Molecular analysis of animal models and patients with Beckwith-Wiedemann Syndrome have shown its nodal implication in the pathogenesis of this syndrome. p57(KIP2) is frequently down-regulated in many common human malignancies through several mechanisms, denoting its anti-oncogenic function. This review is a thorough analysis of data available on p57(KIP2), in relation to p21(CIP1/WAF1) and p27(KIP1), on gene and protein structure, its transcriptional and translational regulation, and its role in human physiology and pathology, focusing on cancer development.
p57(KIP2) 是位于染色体 11p15.5 位置上的一个印迹基因。它是一种细胞周期蛋白依赖性激酶抑制剂，属于 CIP/KIP 家族，该家族还包括 p21(CIP1/WAF1)和 p27(KIP1)。它是 CIP/KIP 家族中研究最少的成员，在胚胎发生中具有独特的作用。p57(KIP2) 调节细胞周期，尽管已经赋予了该蛋白包括细胞骨架组织的新功能。对动物模型和 Beckwith-Wiedemann 综合征患者的分子分析表明，它在该综合征的发病机制中起着关键作用。p57(KIP2) 通过多种机制在许多常见的人类恶性肿瘤中下调，表明其具有抗癌功能。本综述是对与 p21(CIP1/WAF1)和 p27(KIP1)相关的 p57(KIP2)的基因和蛋白结构、转录和翻译调控及其在人类生理学和病理学中的作用的深入分析，重点关注癌症的发展。
