Killin (KLLN)

Killin is a p53-regulated nuclear inhibitor of DNA synthesis, which lies in close proximity to pten on human chromosome 10 and encodes a 20-kDa nuclear protein. Killin is not only necessary but also sufficient for p53-induced apoptosis. Genetic and biochemical analysis demonstrates that Killin is a high-affinity DNA-binding protein, which potently inhibits eukaryotic DNA synthesis in vitro and appears to trigger S phase arrest before apoptosis in vivo. The DNA-binding domain essential for DNA synthesis inhibition was mapped to within 42 amino acid residues near the N terminus of Killin.These results support Killin as a missing link between p53 activation and S phase checkpoint control designed to eliminate replicating precancerous cells, should they escape G(1) blockade mediated by p21.