p57KIP2: "Kip"ing the cell under control

Abstract

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.