DC Field | Value | Language |
---|---|---|
dc.contributor.author | Russo, AA | ko |
dc.contributor.author | Tong, L | ko |
dc.contributor.author | Lee, Jie-Oh | ko |
dc.contributor.author | Jeffrey, PD | ko |
dc.contributor.author | Pavletich, NP | ko |
dc.date.accessioned | 2013-03-02T19:46:29Z | - |
dc.date.available | 2013-03-02T19:46:29Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 1998-09 | - |
dc.identifier.citation | NATURE, v.395, no.6699, pp.237 - 243 | - |
dc.identifier.issn | 0028-0836 | - |
dc.identifier.uri | http://hdl.handle.net/10203/75220 | - |
dc.description.abstract | The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16(INK4a) tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16(INK4a) and to the related p19(INK4d) 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. Ttrmour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16(INK4a). | - |
dc.language | English | - |
dc.publisher | MACMILLAN MAGAZINES LTD | - |
dc.subject | FAMILIAL MELANOMA | - |
dc.subject | CRYSTAL-STRUCTURE | - |
dc.subject | PROTEIN-KINASE | - |
dc.subject | CELLULAR-TRANSFORMATION | - |
dc.subject | RETINOBLASTOMA-PROTEIN | - |
dc.subject | GENE-PRODUCT | - |
dc.subject | TGF-BETA | - |
dc.subject | P16 | - |
dc.subject | MUTATIONS | - |
dc.subject | BINDING | - |
dc.title | Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16(INK4a) | - |
dc.type | Article | - |
dc.identifier.wosid | 000075974600040 | - |
dc.identifier.scopusid | 2-s2.0-0032541623 | - |
dc.type.rims | ART | - |
dc.citation.volume | 395 | - |
dc.citation.issue | 6699 | - |
dc.citation.beginningpage | 237 | - |
dc.citation.endingpage | 243 | - |
dc.citation.publicationname | NATURE | - |
dc.contributor.localauthor | Lee, Jie-Oh | - |
dc.contributor.nonIdAuthor | Russo, AA | - |
dc.contributor.nonIdAuthor | Tong, L | - |
dc.contributor.nonIdAuthor | Jeffrey, PD | - |
dc.contributor.nonIdAuthor | Pavletich, NP | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | FAMILIAL MELANOMA | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURE | - |
dc.subject.keywordPlus | PROTEIN-KINASE | - |
dc.subject.keywordPlus | CELLULAR-TRANSFORMATION | - |
dc.subject.keywordPlus | RETINOBLASTOMA-PROTEIN | - |
dc.subject.keywordPlus | GENE-PRODUCT | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | P16 | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | BINDING | - |
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