Contribution of the dual coding capacity of the p16INK4a/MTS1/CDKN2 locus to human malignancies.
During the three last years, the so-called p16 locus on human chromosome band 9p21 has been increasingly implicated in different cancers by a variety of alterations abolishing both copies of the p16INK4a/MTS1/CDKN2 gene and the adjacent p15INK4b gene, two members of a family of specific inhibitors of the cyclin D 1-3-CDK4/6 complexes that control cell cycle progression of the G1 to S phase. While these properties are characteristic of tumor suppressor genes, abundant experimental data have clearly identified a link between the loss of function of p16INK4a and tumorigenic processes. The role of p15INK4b alterations in the onset of natural and experimental tumors is less obvious. New light may be shed on the role of the p16 locus in tumor development by the recent finding that an alternative transcript from the p16INK4a gene encodes p19ARF, a negative regulator of cell cycle progression which is unrelated to p16 and p15 and does not act by binding any CDK. Hence, this protein appears to be an element of a novel negative cell cycle control mechanism, whose impairing might be involved in tumorigenesis.
Larsen
C J
CJ
INSERM U-301, Institut de Génétique Moléculaire, Paris, France.
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF; D018844:Cyclin-Dependent Kinases