p16(INK4a) and the control of cellular proliferative life span.
Normal somatic cells have a limited proliferative capacity in vitro: after a finite number of cell divisions they eventually enter a non-proliferative state referred to as senescence. Senescence is thought to be a major tumor suppressor mechanism, and many cancers contain cells that have escaped from senescence and become immortalized. The role of telomerase activation in immortalization is currently attracting considerable attention, but immortalization is often associated with other changes including loss of normal function of the tumor suppressor locus, INK4a/ARF. Two proteins, p16(INK4a) and p14(ARF), are encoded by this locus. Here we focus on p16(INK4a) and review accumulating evidence that loss of p16(INK4a) function may be involved in escape from the normal limits on cellular proliferative life span.
Huschtscha
L I
LI
Children's Medical Research Institute, 214 Hawkesbury Rd, Westmead, Sydney, New South Wales 2145, Australia.
Reddel
R R
RR
D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000502:physiology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF
D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF