Telomere dysfunction and tumour suppression: the senescence connection.
Long-lived organisms such as humans have evolved several intrinsic tumour suppressor mechanisms to combat the slew of oncogenic somatic mutations that constantly arise in proliferating stem-cell compartments. One of these anticancer barriers is the telomere, a specialized nucleoprotein complex that caps the ends of eukaryotic chromosome. Impaired telomere function activates the canonical DNA damage response pathway that engages p53 to initiate apoptosis or replicative senescence. Here, we discuss how p53-dependent senescence induced by dysfunctional telomeres may be as potent as apoptosis in suppressing tumorigenesis in vivo.
Deng
Yibin
Y
Department of Cancer Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Chan
Suzanne S
SS
Chang
Sandy
S
D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D004249:DNA Damage; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016160:Retinoblastoma Protein / Q000502:physiology; D019098:Telomerase / Q000502:physiology; D016615:Telomere; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019098:Telomerase