Pathways leading to p53 activation. ATR (ataxia telangiectasia related) is a protein kinase that phosphorylates serine 15. ATM (ataxia telangiectasia mutated) is a protein kinase that phosphorylates serine 15 on p53 and also phosphorylates and activates another protein kinase Chk2. Chk2 is a protein kinase that phosphorylates serine 20. Defects in the CHK2 gene cause a predisposition to cancer. p14ARF is transcriptionally upregulated by aberrant growth signals. p14ARF binds to Mdm2 and blocks its ubiquitination activity. Loss of the p14ARF gene causes Mdm2 to increase in concentration leading to a decrease in the levels of p53.
Note: Ataxia telangiectasia is pronounced "Ay-TACK-see-uh Teh-LAN-jick-TAY-sha."