Cyclin-dependent kinase inhibitor 2A
Kinase inhibitor involved in control of the cell cycle and coded by CDKN2A gene at 9p21. This is a tumour suppressor gene as loss of its function can contribute to carcinogenesis by allowing inappropriate progression through the cell cycle. Its normal function is via two pathways mediated separately by isoform 1 and 4 as a negative regulator of proliferation. Ultimately it stops CDK4 and CDK6 interaction with cyclin D in the P53 pathway and in the retinoblastoma pathway the phosphorylation of the retinoblastoma protein. There are 4 isoforms:
- p16INK4a - or most of the alternative names above for cyclin-dependent kinase inhibitor
- missing first 51 of the 156 amino acids in isoform 1.
- p14ARF, p19ARF, ARF - binds the p53-stabilizing protein MDM2
Surrogate marker in squamous cell cancers where HPV infection is thought to contribute, e.g. gynaecological and oropharyngeal tumours.
Place in pathways
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