View source for 6wxk


==PHF23 PHD Domain Apo==
<StructureSection load='6wxk' size='340' side='right'caption='[[6wxk]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wxk]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WXK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6wxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wxk OCA], [https://pdbe.org/6wxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wxk RCSB], [https://www.ebi.ac.uk/pdbsum/6wxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wxk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PHF23_HUMAN PHF23_HUMAN] A chromosomal aberration involving PHF23 is found in a patient with acute myeloid leukemia (AML). Translocation t(11;17)(p15;p13) with NUP98.
== Function ==
[https://www.uniprot.org/uniprot/PHF23_HUMAN PHF23_HUMAN] Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria.<ref>PMID:25484098</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Chromosomal NUP98-PHF23 translocation is associated with an aggressive form of acute myeloid leukemia (AML) and poor survival rate. Here, we report the molecular mechanisms by which NUP98-PHF23 recognizes the histone mark H3K4me3 and is inhibited by small molecule compounds, including disulfiram that directly targets the PHD finger of PHF23 (PHF23PHD). Our data support a critical role for the PHD fingers of NUP98-PHF23, and related NUP98-KDM5A and NUP98-BPTF fusions in driving leukemogenesis, and demonstrate that blocking this interaction in NUP98-PHF23 expressing AML cells leads to cell death through necrotic and late apoptosis pathways. An overlap of NUP98-KDM5A oncoprotein binding sites and H3K4me3-positive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq, together with NMR analysis of the H3K4me3-binding sites of the PHD fingers from PHF23, KDM5A and BPTF, suggests a common PHD finger-dependent mechanism that promotes leukemogenesis by this type of NUP98 fusions. Our findings highlight the direct correlation between the abilities of NUP98-PHD finger fusion chimeras to associate with H3K4me3-enriched chromatin and leukemic transformation.

Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion.,Zhang Y, Guo Y, Gough SM, Zhang J, Vann KR, Li K, Cai L, Shi X, Aplan PD, Wang GG, Kutateladze TG Nat Commun. 2020 Jul 3;11(1):3339. doi: 10.1038/s41467-020-17098-4. PMID:32620764<ref>PMID:32620764</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wxk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kutateladze T]]
[[Category: Vann KR]]
[[Category: Zhang J]]
[[Category: Zhang Y]]