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PMID:8242750

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Citation

Gyuris, J, Golemis, E, Chertkov, H and Brent, R (1993) Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75:791-803

Abstract

We used the interaction trap, a yeast genetic selection for interacting proteins, to isolate human cyclin-dependent kinase interactor 1 (Cdi1). In yeast, Cdi1 interacts with cyclin-dependent kinases, including human Cdc2, Cdk2, and Cdk3, but not with Ckd4. In HeLa cells, Cdi1 is expressed at the G1 to S transition, and the protein forms stable complexes with Cdk2. Cdi1 bears weak sequence similarity to known tyrosine and dual specificity phosphatases. In vitro, Cdi1 removes phosphate from tyrosine residues in model substrates, but a mutant protein that bears a lesion in the putative active site cysteine does not. Overexpression of wild-type Cdi1 delays progression through the cell cycle in yeast and HeLa cells; delay is dependent on Cdi1 phosphatase activity. These experiments identify Cdi1 as a novel type of protein phosphatase that forms complexes with cyclin-dependent kinases.

Links

PubMed

Keywords

Amino Acid Sequence; Base Sequence; CDC2-CDC28 Kinases; Cell Cycle; Cell Cycle Proteins; Cloning, Molecular/methods; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor Proteins; Cyclin-Dependent Kinases; Cyclins/physiology; DNA, Complementary/genetics; Dual-Specificity Phosphatases; Gene Expression; HeLa Cells; Humans; Molecular Sequence Data; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Protein Binding; Protein Kinase Inhibitors; Protein Kinases/metabolism; Protein Tyrosine Phosphatases; Protein-Serine-Threonine Kinases; RNA, Messenger/genetics; Saccharomyces cerevisiae/genetics; Sequence Alignment; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CDK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16667

F

Seeded From UniProt

complete

HUMAN:CDKN3

involved_in

GO:0051726: regulation of cell cycle

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDKN3

acts_upstream_of_or_within

GO:0051726: regulation of cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDKN3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P24941

F

Seeded From UniProt

complete

HUMAN:CDKN3

involved_in

GO:0000079: regulation of cyclin-dependent protein serine/threonine kinase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDKN3

involved_in

GO:0007050: cell cycle arrest

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDKN3

enables

GO:0008138: protein tyrosine/serine/threonine phosphatase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CDKN3

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDKN3

enables

GO:0004725: protein tyrosine phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CDKN3

involved_in

GO:0007050: cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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