Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.
The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. By use of a yeast interaction screen to search for CDK6-interacting ... proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B). Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Recombinant p18 inhibits the kinase activity of cyclin D-CDK6. Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Ectopic expression of p18 or p16 suppresses cell growth with a correlated dependence on endogenous wild-type pRb.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Cycle Proteins, Cell Division, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 1, Cloning, Molecular, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p18, Cyclin-Dependent Kinases, DNA Primers, Enzyme Inhibitors, Female, Fungal Proteins, Humans, Keratinocytes, Molecular Sequence Data, Nuclear Proteins, Placenta, Pregnancy, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, RNA-Binding Proteins, Retinoblastoma Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Proteins, Vesicular Transport Proteins
Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Cycle Proteins, Cell Division, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 1, Cloning, Molecular, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p18, Cyclin-Dependent Kinases, DNA Primers, Enzyme Inhibitors, Female, Fungal Proteins, Humans, Keratinocytes, Molecular Sequence Data, Nuclear Proteins, Placenta, Pregnancy, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, RNA-Binding Proteins, Retinoblastoma Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Proteins, Vesicular Transport Proteins
Genes Dev.
Date: Dec. 15, 1994
PubMed ID: 8001816
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