Tumor suppressors and oncogenes in cellular senescence.
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.
Bringold
F
F
Department of Immunology and Oncology, National Center of Biotechnology, E-28049, Cantoblanco, Madrid, Spain.
Serrano
M
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009857:Oncogenes; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D011506:Proteins / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D011506:Proteins; D016160:Retinoblastoma Protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human