p16INK4a as a second effector of the telomere damage pathway.
Telomere damage resulting from telomere shortening can potentially suppress tumorigenesis by permanently arresting or eliminating incipient cancer cells. Dysfunctional telomeres activate the canonical DNA damage response pathway, resulting in a p53-mediated G(1)/S arrest and senescence or apoptosis. Experimental induction of telomere damage through inhibition of the telomeric protein TRF2 recapitulates aspects of telomere attrition, including a p53-mediated cell cycle arrest. Using this system, we have shown that telomere damage can also elicit a G(1)/S arrest through the RB-regulator p16INK4a, especially in cells lacking p53 function. Here we discuss the significance of p16INK4a as a second effector of the telomere damage response.
Jacobs
Jacqueline J L
JJ
Deptartment of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
de Lange
Titia
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D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53