Tumor suppression by Ink4a-Arf: progress and puzzles.
The two products of the Ink4a-Arf locus, p16(Ink4a) and p19(Arf) (p14(ARF) in humans), are potent tumor suppressors that regulate the activities of the retinoblastoma protein and the p53 transcription factor. These proteins form part of a signaling network that is disrupted in most, if not all, cancer cells. The Ink4a-Arf locus responds to stress signals, limiting cell proliferation and modulating oncogene-induced apoptosis. Recent evidence emerging from mouse tumor models distinguishes the activities of p16(Ink4a) and p19(Arf) in regulating tumor onset and identifies differences in their responsiveness to drugs.
Lowe
Scott W
SW
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. lowe@cshl.org
Sherr
Charles J
CJ
D020727:ADP-Ribosylation Factors / Q000502:physiology; D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000517:prevention & control*; D051381:Rats; D016160:Retinoblastoma Protein / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D020727:ADP-Ribosylation Factors