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Biochemistry (Moscow)

, Volume 83, Issue 11, pp 1289–1298 | Cite as

Regulation of Tumor Suppressor Gene CDKN2A and Encoded p16-INK4a Protein by Covalent Modifications

  • Yang Jiao
  • Yunpeng Feng
  • Xiuli WangEmail author
Review
  • 149 Downloads

Abstract

CDKN2A is one of the most studied tumor suppressor genes. It encodes the p16-INK4a protein that plays a critical role in the cell cycle progression, differentiation, senescence, and apoptosis. Mutations in CDKN2A or dysregulation of its functional activity are frequently associated with various types of human cancer. As a cyclin-dependent kinase inhibitor, p16-INK4a forms a complex with cyclin-dependent kinases 4/6 (CDK4/6) thereby competing with cyclin D. It is believed that the helix-turn-helix structures in the content of tandem ankyrin repeats in p16-INK4a are required for the protein interaction with CDK4. Until recently, the mechanisms considered to be involved in the regulation of p16-INK4a functions and cancer development have been mutations in DNA, homozygous or heterozygous gene loss, and methylation of CDKN2A promoter region. In this review, we discuss recent findings on the regulation of p16-INK4a by covalent modifications at both transcriptional and post-translational levels.

Keywords

p16-INK4a modification methylation phosphorylation acetylation 

Abbreviations

ANRIL (gene)

antisense noncoding RNA in the INK4-ARF locus

CDK

cyclin-dependent kinase

HAT

his-tone acetyltransferase

HDAC

histone deacetylase

MSK1

mitogen-and stress-activated protein kinase 1

PcG

Polycomb group proteins

PRC1/2

Polycomb repressive complex 1/2

PRMT

protein arginine methyltransferase

Rb

retinoblastoma

RD

regulatory sequence of the INK4-ARF locus

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.School of Physical EducationNortheast Normal UniversityChangchun, JilinP. R. China
  2. 2.Key Laboratory of Molecular Epigenetics, Ministry of EducationNortheast Normal UniversityChangchun, JilinP. R. China
  3. 3.Central Laboratory of General Biology, School of Life SciencesNortheast Normal UniversityChangchun, JilinP. R. China

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