OCA at 09:29, 13 February 2019

OCA — Wed, 13 Feb 2019 09:29:32 GMT

←Older revision		Revision as of 09:29, 13 February 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6fzg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==PPAR gamma mutant complex==
		+	<StructureSection load='6fzg' size='340' side='right' caption='[[6fzg]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6fzg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FZG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDK:(2~{S})-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[[2-(phenylcarbonyl)phenyl]amino]propanoic+acid'>EDK</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=6fzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fzg OCA], [http://pdbe.org/6fzg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fzg RCSB], [http://www.ebi.ac.uk/pdbsum/6fzg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fzg ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN]] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref> Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[http://omim.org/entry/604367 604367]]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref> Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN]] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The upregulation of PPARgamma/RXRalpha transcriptional activity has emerged as a key event in luminal bladder tumors. It renders tumor cell growth PPARgamma-dependent and modulates the tumor microenvironment to favor escape from immuno-surveillance. The activation of the pathway has been linked to PPARG gains/amplifications resulting in PPARgamma overexpression and to recurrent activating point mutations of RXRalpha. Here, we report recurrent mutations of PPARgamma that also activate the PPARgamma/RXRalpha pathway, conferring PPARgamma-dependency and supporting a crucial role of PPARgamma in luminal bladder cancer. These mutations are found throughout the protein-including N-terminal, DNA-binding and ligand-binding domains-and most of them enhance protein activity. Structure-function studies of PPARgamma variants with mutations in the ligand-binding domain allow identifying structural elements that underpin their gain-of-function. Our study reveals genomic alterations of PPARG that lead to pro-tumorigenic PPARgamma/RXRalpha pathway activation in luminal bladder tumors and may open the way towards alternative options for treatment.

-	~~Authors~~:	+	Recurrent activating mutations of PPARgamma associated with luminal bladder tumors.,Rochel N, Krucker C, Coutos-Thevenot L, Osz J, Zhang R, Guyon E, Zita W, Vanthong S, Hernandez OA, Bourguet M, Badawy KA, Dufour F, Peluso-Iltis C, Heckler-Beji S, Dejaegere A, Kamoun A, de Reynies A, Neuzillet Y, Rebouissou S, Beraud C, Lang H, Massfelder T, Allory Y, Cianferani S, Stote RH, Radvanyi F, Bernard-Pierrot I Nat Commun. 2019 Jan 16;10(1):253. doi: 10.1038/s41467-018-08157-y. PMID:30651555<ref>PMID:30651555</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6fzg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Rochel, N]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Transcription]]

OCA: Protected "6fzg" [edit=sysop:move=sysop]

OCA — Wed, 21 Mar 2018 06:23:00 GMT

Protected "6fzg" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:23, 21 March 2018

OCA: New page: '''Unreleased structure''' The entry 6fzg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 21 Mar 2018 06:22:59 GMT

New page: '''Unreleased structure''' The entry 6fzg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6fzg is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]

6fzg - Revision history

OCA at 09:29, 13 February 2019

OCA: Protected "6fzg" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6fzg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures