1ap7

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1ap7

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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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