The p16(INK4a) and p14(ARF) tumor suppressor genes (TSGs) are encoded within the CDKN2A locus on chromosome 9p21 and function as cell cycle regulatory proteins in the p53 and RB pathways.
Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases.
To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model induced by ischaemia reperfusion (I/R) in wild-type (ASPP2<sup>+/+</sup> ) mice and ASPP2 haploinsufficient (ASPP2<sup>+/-</sup> ) mice.
Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD.
We find that p53 was upregulated in cisplatin-induced AKI, yet, pifithrin-α inhibites the p53 expression to attenuated renal injury and cell apoptosis both in vivo cisplatin-induced AKI mice and in vitro HK-2 human renal tubular epithelial cells.
We have examined how disease progression correlates with changes in expression of the p14ARF (ARF) tumour suppressor, a key regulator of the p53 tumour suppressor pathway that is silenced in some 30% of cancers overall, but for which a role in oesophageal cancer is unclear.
We report here that NO induces the accumulation of transcriptionally active p53 in a variety of cell types and that NO signaling to p53 does not require ataxia telangiectasia-mutated (ATM), poly(ADP-ribose) polymerase 1, or the ARF tumor suppressor protein.