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2m1r

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Revision as of 10:26, 10 September 2015

PHD domain of ING4 N214D mutant

Structural highlights

2m1r is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2k1j, 2vnf, 4afl, 1pnx
Gene:	ING4, My036 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[ING4_HUMAN] Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC. Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Inhibitor of growth 4 (ING4) is a member of the ING family of tumor suppressor proteins. In this study, we have analyzed the impact of two mutations in ING4 associated with human tumors (Y121N and N214D), testing their behavior in a series of functional, biochemical and structural analyses. We report that the N214D mutation dramatically dampened the ability of ING4 to inhibit proliferation, anchorage-independent growth or cell migration or to sensitize to cell death. In turn, the Y121N mutant did not differ significantly from wild-type ING4 in our assays. Neither of the mutations altered the normal subcellular localization of ING4, showing predominantly nuclear accumulation. We investigated the molecular basis of the defect in the activity of the N214D mutant. The folding and ability to bind histone marks of ING4 was not significantly altered by this mutation. Instead, we found that the functional impairment of the N214D mutant correlates with reduced protein stability due to increased proteasome-mediated degradation. In summary, our data demonstrates that a point mutation of ING4 associated to human tumors leads to the loss of several essential functions of ING4 pertinent to tumor protection and highlight the importance of ING4 function to prevent tumorigenesis.

Functional impact of cancer-associated mutations in the tumor suppressor protein ING4.,Moreno A, Palacios A, Orgaz JL, Jimenez B, Blanco FJ, Palmero I Carcinogenesis. 2010 Nov;31(11):1932-8. doi: 10.1093/carcin/bgq171. Epub 2010 Aug, 12. PMID:20705953^[7]

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

References

↑ Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, Onogi H, Higashimoto Y, Appella E, Yokota J, Harris CC. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 2003 May 15;63(10):2373-8. PMID:12750254
↑ Zhang X, Xu LS, Wang ZQ, Wang KS, Li N, Cheng ZH, Huang SZ, Wei DZ, Han ZG. ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells. FEBS Lett. 2004 Jul 16;570(1-3):7-12. PMID:15251430 doi:http://dx.doi.org/10.1016/j.febslet.2004.06.010
↑ Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK. The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature. 2004 Mar 18;428(6980):328-32. PMID:15029197 doi:http://dx.doi.org/10.1038/nature02329
↑ Kim S, Chin K, Gray JW, Bishop JM. A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer. Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16251-6. Epub 2004 Nov 4. PMID:15528276 doi:http://dx.doi.org/10.1073/pnas.0407158101
↑ Ozer A, Wu LC, Bruick RK. The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF). Proc Natl Acad Sci U S A. 2005 May 24;102(21):7481-6. Epub 2005 May 16. PMID:15897452 doi:0502716102
↑ Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. PMID:16387653 doi:10.1016/j.molcel.2005.12.007
↑ Moreno A, Palacios A, Orgaz JL, Jimenez B, Blanco FJ, Palmero I. Functional impact of cancer-associated mutations in the tumor suppressor protein ING4. Carcinogenesis. 2010 Nov;31(11):1932-8. doi: 10.1093/carcin/bgq171. Epub 2010 Aug, 12. PMID:20705953 doi:http://dx.doi.org/10.1093/carcin/bgq171

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m1r"

@@ Line 2: / Line 2: @@
 <StructureSection load='2m1r' size='340' side='right' caption='[[2m1r]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m1r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M1R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m1r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M1R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M1R FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2k1j|2k1j]], [[2vnf|2vnf]], [[4afl|4afl]], [[1pnx|1pnx]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ING4, My036 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ING4, My036 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2m1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m1r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2m1r RCSB], [http://www.ebi.ac.uk/pdbsum/2m1r 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=2m1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m1r OCA], [http://pdbe.org/2m1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m1r RCSB], [http://www.ebi.ac.uk/pdbsum/2m1r PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2m1r" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Blanco, F J]]
 [[Category: Gene regulation]]

2m1r

From Proteopedia

Revision as of 10:26, 10 September 2015

PHD domain of ING4 N214D mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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