1ap7
From Proteopedia
(New page: 200px<br /><applet load="1ap7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ap7" /> '''P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES'''<...) |
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| - | [[Image:1ap7.gif|left|200px]]<br /><applet load="1ap7" size=" | + | [[Image:1ap7.gif|left|200px]]<br /><applet load="1ap7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ap7" /> | caption="1ap7" /> | ||
'''P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES'''<br /> | '''P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In cancer, the biochemical pathways that are dominated by the two | + | In cancer, the biochemical pathways that are dominated by the two tumour-suppressor proteins, p53 and Rb, are the most frequently disrupted. Cyclin D-dependent kinases phosphorylate Rb to control its activity and they are, in turn, specifically inhibited by the Ink4 family of cyclin-dependent kinase inhibitors (CDKIs) which cause arrest at the G1 phase of the cell cycle. Mutations in Rb, cyclin D1, its catalytic subunit Cdk4, and the CDKI p16Ink4a, which alter the protein or its level of expression, are all strongly implicated in cancer. This suggests that the Rb 'pathway' is of particular importance. Here we report the structure of the p19Ink4d protein, determined by NMR spectroscopy. The structure indicates that most mutations to the p16Ink4a gene, which result in loss of function, are due to incorrectly folded and/or insoluble proteins. We propose a model for the interaction of Ink4 proteins with D-type cyclin-Cdk4/6 complexes that might provide a basis for the design of therapeutics against cancer. The sequences of the Ink4 family of CDKIs are highly conserved |
==About this Structure== | ==About this Structure== | ||
| - | 1AP7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1AP7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AP7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Archer, S | + | [[Category: Archer, S J.]] |
| - | [[Category: Domaille, P | + | [[Category: Domaille, P J.]] |
| - | [[Category: Laue, E | + | [[Category: Laue, E D.]] |
| - | [[Category: Luh, F | + | [[Category: Luh, F Y.]] |
| - | [[Category: Smith, B | + | [[Category: Smith, B O.]] |
[[Category: ankyrin repeat]] | [[Category: ankyrin repeat]] | ||
[[Category: cdki]] | [[Category: cdki]] | ||
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[[Category: ink]] | [[Category: ink]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:46:53 2008'' |
Revision as of 09:46, 21 February 2008
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P19-INK4D FROM MOUSE, NMR, 20 STRUCTURES
Overview
In cancer, the biochemical pathways that are dominated by the two tumour-suppressor proteins, p53 and Rb, are the most frequently disrupted. Cyclin D-dependent kinases phosphorylate Rb to control its activity and they are, in turn, specifically inhibited by the Ink4 family of cyclin-dependent kinase inhibitors (CDKIs) which cause arrest at the G1 phase of the cell cycle. Mutations in Rb, cyclin D1, its catalytic subunit Cdk4, and the CDKI p16Ink4a, which alter the protein or its level of expression, are all strongly implicated in cancer. This suggests that the Rb 'pathway' is of particular importance. Here we report the structure of the p19Ink4d protein, determined by NMR spectroscopy. The structure indicates that most mutations to the p16Ink4a gene, which result in loss of function, are due to incorrectly folded and/or insoluble proteins. We propose a model for the interaction of Ink4 proteins with D-type cyclin-Cdk4/6 complexes that might provide a basis for the design of therapeutics against cancer. The sequences of the Ink4 family of CDKIs are highly conserved
About this Structure
1AP7 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structure of the cyclin-dependent kinase inhibitor p19Ink4d., Luh FY, Archer SJ, Domaille PJ, Smith BO, Owen D, Brotherton DH, Raine AR, Xu X, Brizuela L, Brenner SL, Laue ED, Nature. 1997 Oct 30;389(6654):999-1003. PMID:9353127
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