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Somatic cells show a spontaneous decline in growth rate on continuous culture, related not to elapsed time but to an increasing number of population doublings, eventually terminating in a quiescent but viable state, termed replicative senescence. These cells are commonly multinucleated and do not respond to mitogens or apoptotic stimuli. Cells displaying characteristics of senescent cells can also...
The ARF protein is a key mediator of the activation of the p53 tumor suppressor in response to excessive mitogenic signals. ARF is encoded in the INK4a/ARF locus, together with the cell-cycle inhibitor p16INK4a. Mice genetically deficient for ARF show a marked predisposition to tumor formation, supporting an important role for ARF in tumor protection. Alterations of the INK4a/ARF locus are a highly...
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