Cloning and characterization of murine p16INK4a and p15INK4b genes

D E Quelle; R A Ashmun; G J Hannon; P A Rehberger; D Trono; K H Richter; C Walker; D Beach; C J Sherr; M Serrano

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Cloning and characterization of murine p16INK4a and p15INK4b genes

Journal article

Peer reviewed

Cloning and characterization of murine p16INK4a and p15INK4b genes

D E Quelle, R A Ashmun, G J Hannon, P A Rehberger, D Trono, K H Richter, C Walker, D Beach, C J Sherr and M Serrano

Oncogene, Vol.11(4), pp.635-645

08/17/1995

PMID: 7651726

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Abstract

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 p16INK4a and p15INK4b based on their homology to their human counterparts and their selective transcriptional induction by SV40T-antigen and TGF-beta, 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 p16INK4a in many normal tissues, whereas p15INK4b was expressed ubiquitously. Like human p16INK4a, mouse p16INK4a binds specifically to cdk4 and cdk6 in vitro and inhibits the phosphorylation of the retinoblastoma protein, pRb, by each of these cyclin D-dependent kinases. In mouse MEL erythroleukemia cells, p16INK4a associates preferentially with cdk6 under conditions where cdk4 and cdk6 are coexpressed at equivalent levels. Expression vectors encoding human or mouse p16INK4a caused G1 phase arrest in NIH3T3 fibroblasts, and cyclin D1- and cdk4-dependent pRb kinase activities were inhibited in the p16INK4a-arrested cells.

Transfection

Polymerase Chain Reaction

Gene Expression

Cell Cycle - genetics

Humans

Cyclin-Dependent Kinase Inhibitor p15

Molecular Sequence Data

Chromosome Disorders

Cyclin-Dependent Kinase Inhibitor p16

Base Sequence

Cloning, Molecular

Amino Acid Sequence

Cell Line

Mice - genetics

Carrier Proteins - biosynthesis

In Situ Hybridization, Fluorescence

Chromosome Mapping

Chromosomes, Human, Pair 9

DNA Primers

Sequence Homology, Amino Acid

Carrier Proteins - genetics

G1 Phase

Protein Kinase Inhibitors

Animals

Chromosome Aberrations

3T3 Cells

Cell Cycle Proteins

Tumor Suppressor Proteins

Details

Title: Subtitle: Cloning and characterization of murine p16INK4a and p15INK4b genes
Creators: D E Quelle - Howard Hughes Medical Institute, Memphis, Tennessee, USA
R A Ashmun
G J Hannon
P A Rehberger
D Trono
K H Richter
C Walker
D Beach
C J Sherr
M Serrano
Resource Type: Journal article
Publication Details: Oncogene, Vol.11(4), pp.635-645
Publisher: England
PMID: 7651726
ISSN: 0950-9232
eISSN: 1476-5594
Grant note: R01-CA63613 / NCI NIH HHS CA-47064 / NCI NIH HHS
Language: English
Date published: 08/17/1995
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984040476802771

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