Functional Versatility of the CDK Inhibitor p57Kip2

Justine Creff; Arnaud Besson

doi:10.3389/fcell.2020.584590

Functional Versatility of the CDK Inhibitor p57^Kip2

Front Cell Dev Biol. 2020 Oct 7:8:584590. doi: 10.3389/fcell.2020.584590. eCollection 2020.

Authors

Justine Creff¹, Arnaud Besson¹

Affiliation

¹ Centre National de la Recherche Scientifique, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Centre de Biologie Intégrative, Université de Toulouse, Toulouse, France.

Abstract

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.

Keywords: CDK inhibitor; CDKN1C; cell cycle; development; p57Kip2; stem cells; transcription.

Publication types

Review