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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
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Genes, Tumor Suppressor*
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Genes, p53
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Humans
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Melanoma / genetics
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Neoplasms / genetics*
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Neoplasms / metabolism
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Nuclear Proteins*
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-mdm2
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism
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Tumor Suppressor Protein p14ARF
Substances
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Cyclin-Dependent Kinase Inhibitor p16
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Tumor Suppressor Protein p14ARF
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2