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  • Title: The INK4a/ARF tumor suppressor: one gene--two products--two pathways.
    Author: Chin L, Pomerantz J, DePinho RA.
    Journal: Trends Biochem Sci; 1998 Aug; 23(8):291-6. PubMed ID: 9757829.
    Abstract:
    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.
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