Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4aand p19ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1
Copyright policy )Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4aand p19ARF, is a candidate for the plasmacytoma susceptibility locus,Pctr1
Plasma cell tumor induction in mice by pristane is under multigenic control. BALB/c mice are susceptible to tumor development; whereas DBA/2 mice are resistant. Restriction fragment length polymorphisms between BALB/c and DBA/2 forCdkn2a(p16) andCdkn2b(p15), and between BALB/c andMus spretusforCdkn2c(p18INK4c) were used to position these loci with respect to thePctr1locus. These cyclin-dependent kinase (CDK) inhibitors mapped to a 6 cM interval of chromosome 4 betweenIfnaandTal1. C.D2-Chr 4 congenic strains harboring DBA/2 alleles associated with thePctr1locus contained DBA/2 “resistant” alleles of the CDK4/CDK6 inhibitors p16 and p15. On sequencing p16 and p18 cDNAs, two different allelic variants within ankyrin repeat regions of p16 were found between BALB/c and DBA/2 mice. By using an assay involving PCR amplification and restriction enzyme digestion, allelic variants were typed among several inbred strains of mice. One of the variants, G232A, was specific to two inbred strains, BALB/cAn and ABP/Le, of mice and occurred in a highly conserved amino acid in both human and rat p16. When tested with wild-type (DBA/2) p16, both A134C and G232A BALB/c-specific variants of p16 were inefficient in their ability to inhibit the activity of cyclin D2/CDK4 in kinase assays with retinoblastoma protein, suggesting this defective, inherited allele plays an important role in the genetic susceptibility of BALB/c mice for plasmacytoma induction and that p16INK4ais a strong candidate for thePctr1locus.
- National Cancer Institute United States
- National Institute of Health Pakistan
- National Institutes of Health United States
Ankyrins, Male, Mice, Inbred BALB C, Genes, p16, Molecular Sequence Data, Chromosome Mapping, Cell Cycle Proteins, Muridae, Mice, Mice, Inbred DBA, Animals, Humans, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Amino Acid Sequence, Carrier Proteins, Crosses, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p15
Ankyrins, Male, Mice, Inbred BALB C, Genes, p16, Molecular Sequence Data, Chromosome Mapping, Cell Cycle Proteins, Muridae, Mice, Mice, Inbred DBA, Animals, Humans, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Amino Acid Sequence, Carrier Proteins, Crosses, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p15
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