A p18 mutant defective in CDK6 binding in human breast cancer cells.
Progression from G1 to the S-phase of the cell cycle is controlled by a family of low molecular weight cyclin-dependent kinase (CDK) inhibitors. The importance of these proteins in cell growth control is underscored by the observation that some members of this family are deleted or mutated in human cancers. For example, the gene encoding the CDK inhibitor p18 is located on a segment of chromosome 1 that is often abnormal in human breast tumors. We have identified an alanine to proline substitution at codon 72 of the p18 gene in BT-20 human breast cancer cells. This mutation abrogates the ability of p18 to interact with CDK6 and renders p18 deficient in suppressing cell growth in a colony formation assay. Our results suggest that p18 inactivation by point mutations may contribute to deregulated growth control in certain cell lines and/or tumors.
Lapointe
J
J
Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, Canada.
Lachance
Y
Y
Labrie
Y
Y
Labrie
C
C
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493971:CDKN2C protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D005982:Glutathione Transferase; D018844:Cyclin-Dependent Kinases