Abstract
Cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), and p27(Kip1) are regarded as key effectors of cellular senescence. In this review, we describe three senescence-inducing pathways involving these inhibitors, namely, the p16(INK4a)/Rb pathway, the p19(ARF)/p53/p21(Cip1) pathway, and the PTEN/p27(Kip1) pathway. We emphasize the participation of tumor suppressors and oncogenes in the regulation of these senescence-inducing pathways. Finally, we discuss the impact of the Ras and Myc oncogenes on the above-mentioned pathways.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Apoptosis / genetics
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Cell Cycle Proteins*
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Cellular Senescence / genetics*
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Cellular Senescence / physiology
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Cyclin-Dependent Kinase Inhibitor p16 / physiology
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclins / physiology
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Enzyme Inhibitors / metabolism
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Genes, Retinoblastoma
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Genes, Tumor Suppressor*
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Genes, myc
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Genes, p53
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Genes, ras
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Humans
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Microtubule-Associated Proteins / physiology
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Oncogenes*
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / physiology
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Proteins / physiology
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Retinoblastoma Protein / physiology
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53 / physiology
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Tumor Suppressor Proteins*
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Microtubule-Associated Proteins
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Proteins
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Retinoblastoma Protein
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human