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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6699
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pubmed:dateCreated |
1998-10-15
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pubmed:databankReference |
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pubmed:abstractText |
The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. They prevent cyclin binding indirectly by causing structural changes that propagate to the cyclin-binding site. The INK4 inhibitors also distort the kinase catalytic cleft and interfere with ATP binding, which explains how they can inhibit the preassembled Cdk4/6-cyclin D complexes as well. Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/CDK6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN2D protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
395
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
237-43
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9751050-Adenosine Triphosphate,
pubmed-meshheading:9751050-Amino Acid Sequence,
pubmed-meshheading:9751050-Binding Sites,
pubmed-meshheading:9751050-Carrier Proteins,
pubmed-meshheading:9751050-Cell Cycle Proteins,
pubmed-meshheading:9751050-Crystallography, X-Ray,
pubmed-meshheading:9751050-Cyclin D,
pubmed-meshheading:9751050-Cyclin-Dependent Kinase 6,
pubmed-meshheading:9751050-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:9751050-Cyclin-Dependent Kinase Inhibitor p19,
pubmed-meshheading:9751050-Cyclin-Dependent Kinases,
pubmed-meshheading:9751050-Cyclins,
pubmed-meshheading:9751050-Enzyme Inhibitors,
pubmed-meshheading:9751050-Escherichia coli,
pubmed-meshheading:9751050-Genes, Tumor Suppressor,
pubmed-meshheading:9751050-Humans,
pubmed-meshheading:9751050-Models, Molecular,
pubmed-meshheading:9751050-Molecular Sequence Data,
pubmed-meshheading:9751050-Protein Binding,
pubmed-meshheading:9751050-Protein Conformation,
pubmed-meshheading:9751050-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9751050-Recombinant Proteins,
pubmed-meshheading:9751050-Structure-Activity Relationship
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pubmed:year |
1998
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pubmed:articleTitle |
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a.
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pubmed:affiliation |
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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