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1blx

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Revision as of 08:06, 11 September 2015

P19INK4D/CDK6 COMPLEX

Structural highlights

1blx is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[CDK6_HUMAN] Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] [CDN2D_MOUSE] Interacts strongly with CDK4 and CDK6 and inhibits them.^[10] ^[11]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19 INK4d protein has been determined at 1.9 A resolution. The results provide the first structural information for a cyclin D-dependent protein kinase and show how the INK4 family of CDK inhibitors bind. The structure indicates that the conformational changes induced by p19INK4d inhibit both productive binding of ATP and the cyclin-induced rearrangement of the kinase from an inactive to an active conformation. The structure also shows how binding of an INK4 inhibitor would prevent binding of p27Kip1, resulting in its redistribution to other CDKs. Identification of the critical residues involved in the interaction explains how mutations in Cdk4 and p16INK4a result in loss of kinase inhibition and cancer.

Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d.,Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ, Serrano M, Brenner SL, Blundell TL, Laue ED Nature. 1998 Sep 17;395(6699):244-50. PMID:9751051^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Meyerson M, Harlow E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol. 1994 Mar;14(3):2077-86. PMID:8114739
↑ Matushansky I, Radparvar F, Skoultchi AI. CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells. Oncogene. 2003 Jul 3;22(27):4143-9. PMID:12833137 doi:10.1038/sj.onc.1206484
↑ Lucas JJ, Domenico J, Gelfand EW. Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells. Mol Cancer Res. 2004 Feb;2(2):105-14. PMID:14985467
↑ Ogasawara T, Kawaguchi H, Jinno S, Hoshi K, Itaka K, Takato T, Nakamura K, Okayama H. Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6. Mol Cell Biol. 2004 Aug;24(15):6560-8. PMID:15254224 doi:10.1128/MCB.24.15.6560-6568.2004
↑ Takaki T, Fukasawa K, Suzuki-Takahashi I, Semba K, Kitagawa M, Taya Y, Hirai H. Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. J Biochem. 2005 Mar;137(3):381-6. PMID:15809340 doi:10.1093/jb/mvi050
↑ Fujimoto T, Anderson K, Jacobsen SE, Nishikawa SI, Nerlov C. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. EMBO J. 2007 May 2;26(9):2361-70. Epub 2007 Apr 12. PMID:17431401 doi:10.1038/sj.emboj.7601675
↑ Ruas M, Gregory F, Jones R, Poolman R, Starborg M, Rowe J, Brookes S, Peters G. CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms. Mol Cell Biol. 2007 Jun;27(12):4273-82. Epub 2007 Apr 9. PMID:17420273 doi:10.1128/MCB.02286-06
↑ Fiaschi-Taesch NM, Salim F, Kleinberger J, Troxell R, Cozar-Castellano I, Selk K, Cherok E, Takane KK, Scott DK, Stewart AF. Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6. Diabetes. 2010 Aug;59(8):1926-36. doi: 10.2337/db09-1776. PMID:20668294 doi:10.2337/db09-1776
↑ Sarek G, Jarviluoma A, Moore HM, Tojkander S, Vartia S, Biberfeld P, Laiho M, Ojala PM. Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency. PLoS Pathog. 2010 Mar 19;6(3):e1000818. doi: 10.1371/journal.ppat.1000818. PMID:20333249 doi:10.1371/journal.ppat.1000818
↑ Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ. Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol Cell Biol. 1995 May;15(5):2672-81. PMID:7739547
↑ Chan FK, Zhang J, Cheng L, Shapiro DN, Winoto A. Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4. Mol Cell Biol. 1995 May;15(5):2682-8. PMID:7739548
↑ Brotherton DH, Dhanaraj V, Wick S, Brizuela L, Domaille PJ, Volyanik E, Xu X, Parisini E, Smith BO, Archer SJ, Serrano M, Brenner SL, Blundell TL, Laue ED. Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. Nature. 1998 Sep 17;395(6699):244-50. PMID:9751051 doi:http://dx.doi.org/10.1038/26164

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1blx"

@@ Line 2: / Line 2: @@
 <StructureSection load='1blx' size='340' side='right' caption='[[1blx]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1blx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BLX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1blx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BLX FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1blx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1blx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1blx RCSB], [http://www.ebi.ac.uk/pdbsum/1blx PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1blx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1blx OCA], [http://pdbe.org/1blx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1blx RCSB], [http://www.ebi.ac.uk/pdbsum/1blx PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 26: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1blx" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 33: / Line 34: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Archer, S J]]
 [[Category: Blundell, T L]]

1blx

From Proteopedia

Revision as of 08:06, 11 September 2015

P19INK4D/CDK6 COMPLEX

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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