Cloning and characterization of murine p16(INK4a) and p15(INK4b) genes

Quelle, D. E., Ashmun, R. A., Hannon, G. J., Rehberger, P. A., Trono, D., Richter, K. H., Walker, C., Beach, D., Sherr, C. J., Serrano, M. (1995) Cloning and characterization of murine p16(INK4a) and p15(INK4b) genes. Oncogene, 11 (4). pp. 635-645. ISSN 09509232 (ISSN)



Progression through the G1 phase of the cell cycle is regulated in part by the D-type cyclin-dependent kinases, cdk4 and cdk6. Genes encoding two specific inhibitors of these kinases, human p16((INK4a/MTS1)) and p15((INK4b/MTS2)) map to a region of common cytogenetic abnormalities on chromosome 9p21. The murine cognates of these genes were isolated and identified as mouse p16(INK4a) and p15(INK4b) based on their homology to their human counterparts and their selective transcriptional induction by SV40T-antigen and TGF-β, respectively. Both genes map to position C3-C6 on mouse chromosome 4, in a region syntenic with human chromosome 9p. Amplification of polyadenylated mRNA by polymerase chain reactions revealed no expression of mouse p16(INK4a) in, many normal tissues, whereas p15(INK4b) was expressed ubiquitously. Like human p16(INK4a), mouse p16(INK4a) binds specifically to cdk4 and cdk6 in vitro and inhibits the phosporylation of the retinoblastoma protein, pRb, by each of these cyclin D-dependent kinases. In mouse MEL erythroleukemia cells, p16(INK4a) associates preferentially with cdk6 under conditions where cdk4 and cdk6 are coexpressed at equivalent levels. Expression vectors encoding human or mouse p16(INK4a) caused G1 phase arrest in NIH3T3 fibroblasts, and cyclin D1- and cdk4-dependent pRb kinase activities were inhibited in the p16(INK4a)-arrested cells.

Item Type: Paper
Uncontrolled Keywords: cdk D cyclins MEL cells p15(INK4b) p16(INK4a) pRb cyclin dependent kinase polyadenylated rna protein kinase inhibitor retinoblastoma protein transforming growth factor beta virus t antigen animal cell article cell cycle g1 phase cell strain 3t3 chromosome 9p controlled study dna sequence embryo enzyme inhibition erythroleukemia cell fibroblast gene amplification gene expression gene isolation gene mapping genetic analysis molecular cloning mouse nonhuman polymerase chain reaction priority journal protein phosphorylation simian virus 40 transcription initiation 3T3 Cells Amino Acid Sequence Animal Base Sequence Carrier Proteins Cell Cycle Cell Line Chromosome Aberrations Chromosome Disorders Chromosome Mapping Chromosomes, Human, Pair 9 Cloning, Molecular Comparative Study DNA Primers G1 Phase Human In Situ Hybridization, Fluorescence Mice Molecular Sequence Data Protein Kinases Protein p16 Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
Investigative techniques and equipment > cloning
Investigative techniques and equipment > assays > cloning
organism description > animal > mammal > primates > hominids > human
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Beach lab
CSHL labs > Hannon lab
Depositing User: Jessica Koos
Date: 1995
Date Deposited: 11 Aug 2014 15:28
Last Modified: 11 Aug 2014 15:28
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