Functional Versatility of the CDK Inhibitor p57(Kip2)

The cyclin/CDK inhibitor p57(Kip2) belongs to the Cip/Kip family, with p21(Cip1) and p27(Kip1), and is the least studied member of the family. Unlike the other family members, p57(Kip2) has a unique role during embryogenesis and is the only CDK inhibitor required for embryonic development. p57(Kip2) is encoded by the imprinted gene CDKN1C, which is the gene most frequently silenced or mutated in the genetic disorder Beckwith–Wiedemann syndrome (BWS), characterized by multiple developmental anomalies. Although initially identified as a cell cycle inhibitor based on its homology to other Cip/Kip family proteins, multiple novel functions have been ascribed to p57(Kip2) in recent years that participate in the control of various cellular processes, including apoptosis, migration and transcription. Here, we will review our current knowledge on p57(Kip2) structure, regulation, and its diverse functions during development and homeostasis, as well as its potential implication in the development of various pathologies, including cancer.