Genetic and Epigenetic Control of CDKN1C Expression: Importance in Cell Commitment and Differentiation, Tissue Homeostasis and Human Diseases.

The gene encodes the p57 protein which has been identified as the third member of the CIP/Kip family, also including p27 and p21. In analogy with these proteins, p57 is able to bind tightly and inhibit cyclin/cyclin-dependent kinase complexes and, in turn, modulate cell division cycle progression. For a long time, the main function of p57 has been associated only to correct embryogenesis, since -ablated mice are not vital. Accordingly, it has been demonstrated that alterations cause three human hereditary syndromes, characterized by altered growth rate. Subsequently, the p57 role in several cell phenotypes has been clearly assessed as well as its down-regulation in human cancers. lies in a genetic locus, 11p15.5, characterized by a remarkable regional imprinting that results in the transcription of only the maternal allele. The control of transcription is also linked to additional mechanisms, including DNA methylation and specific histone methylation/acetylation. Finally, long non-coding RNAs and miRNAs appear to play important roles in controlling p57 levels. This review mostly represents an appraisal of the available data regarding the control of gene expression. In addition, the structure and function of p57 protein are briefly described and correlated to human physiology and diseases.