Structure of the cyclin-dependent kinase inhibitor p19 Ink4d

Article Abstract:

Biochemical pathways dominated by p53 and Rb, tumour-supressor proteins, are the most often disrupted in cancer. It is suggested that the Rb pathway is of particular significance. The structure of the p19Ink4d protein is reported, using NMR spectroscopy. Its structure suggests that most mutations to the p16Ink4a gene will lead to loss of function because of incorrectly folded or insoluble protein. A model for the interaction of Ink4 proteins with D-type cyclin-Cdk4/6 compounds that could form the basis for the design of cancer therapeutics, is proposed.

Author: Owen, Darerca, Luh, Frederich Y., Archer, Sharon J., Domaille, Peter J., Smith, Brian O., Brotherton, Deborah H., Raine, Andrew R.C., Xu, Xu, Brizuela, Leonardo, Brenner, Stephen L., Laue, Ernest D.
Drug therapy, Observations, Cancer, Tumor suppressor genes

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Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d

Article Abstract:

Cyclin-dependent kinases (CDKs) play an important part in controlling the eukaryotic cell cycle, and are partially activated by their regulatory cyclin subunits. The three-dimensional structure of the p19INK4d/Cdk6 complex has been determined using x-ray diffraction analysis, to gain further knowledge about the regulation of cyclin D-dependent kinases. It is indicated that conformational changes induced by p19INK4d inhibit productive ATP binding and the rearrangement of the kinase to an active conformation.

Author: Serrano, Manuel, Blundell, Tom L., Archer, Sharon J., Domaille, Peter J., Brotherton, Deborah H., Xu, Xu, Brizuela, Leonardo, Brenner, Stephen L., Laue, Ernest D., Dhanaraj, Venugopal, Wick, Scott, Volyanik, Elena, Parisini, Emilio, Smith, Brian, O.
Eukaryotic cells, Cells (Biology), Eukaryotes, Protein kinases, X-rays, X-ray diffraction

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Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK

Article Abstract:

The Cdc42 and Rac proteins are in the Rho family of small GTPases, controlling signal-transduction pathways leading to rearrangements of the cell cytoskeleton, proliferation and differentiation. They bind to downstream effector proteins and these CRIB proteins bind to both Cdc42 and Rac. The ACK tyrosine kinases and the Wiscott-Aldrich-syndrome proteins (WASPs) are specific for Cdc42. The solution structure of the complex of Cdc42 with the GTPase-binding domain of ACK is reported.

Author: Manser, Edward, Lim, Louis, Owen, Darerca, Laue, Ernest D., Mott, Helen R., Nietlispach, Daniel, Lowe, Peter N.
G proteins, Wiskott-Aldrich syndrome

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Subjects list: Research
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