title: The molecular balancing act of p16(INK4a) in cancer and aging.
abstract: p16(INK4a), located on chromosome 9p21.3, is lost among a cluster of neighboring tumor suppressor genes. Although it is classically known for its capacity to inhibit cyclin-dependent kinase (CDK) activity, p16(INK4a) is not just a one-trick pony. Long-term p16(INK4a) expression pushes cells to enter senescence, an irreversible cell-cycle arrest that precludes the growth of would-be cancer cells but also contributes to cellular aging. Importantly, loss of p16(INK4a) is one of the most frequent events in human tumors and allows precancerous lesions to bypass senescence. Therefore, precise regulation of p16(INK4a) is essential to tissue homeostasis, maintaining a coordinated balance between tumor suppression and aging. This review outlines the molecular pathways critical for proper p16(INK4a) regulation and emphasizes the indispensable functions of p16(INK4a) in cancer, aging, and human physiology that make this gene special.
authors.affiliation: Biomedical Research Tower, Rm 586, The Ohio State University, 460 W. 12th Avenue, Columbus, OH 43210. burd.25@osu.edu.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: LaPak
authors.forename: Christin E
authors.initials: CE
authors.lastname: Burd
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016922:Cellular Senescence; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16