The INK4a/ARF tumor suppressor: one gene--two products--two pathways.
Functional inactivation of the retinoblastoma (RB) and p53 pathways appears to be a rite of passage for all cancerous cells and results in disruption of cell-cycle regulation and deactivation of the apoptotic response that normally ensues. The INK4a/ARF locus sits at the nexus of these two growth-control pathways, by virtue of its ability to generate two distinct products: the p16INK4a protein, a cyclin-dependent kinase inhibitor that functions upstream of RB; and the p19ARF protein, which blocks MDM2 inhibition of p53 activity. This 'one gene--two products--two pathways' arrangement provides a basis for the prominence of INK4a/ARF in tumorigenesis.
Chin
L
L
Dept of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Pomerantz
J
J
DePinho
R A
RA
D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D008545:Melanoma / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF
D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2