5ety - Revision history

OCA at 09:11, 20 March 2024

2024-03-20T09:11:26Z

←Older revision		Revision as of 09:11, 20 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_HUMAN] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>		[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_HUMAN] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The Wnt/beta-catenin pathway is a well-known oncogenic pathway. Its suppression has long been considered as an important challenge in treating cancer patients. Among colon cancer patients in particular, most patients carry an adenomatous polyposis coli (APC) mutation that leads to an aberration of Wnt/beta-catenin pathway. To discover the small molecule inhibitors of the Wnt/beta-catenin pathway, we conducted high-throughput screening in APC-mutant colon cancer DLD-1 cells using a transcriptional reporter assay, which identified a selective Wnt/beta-catenin pathway inhibitor, K-756. K-756 stabilizes Axin and reduces active beta-catenin, and inhibits the genes downstream of endogenous Wnt/beta-catenin. We subsequently identified that K-756 is a tankyrase (TNKS) inhibitor. TNKS, which belongs to the PARP family, poly-ADP ribosylates Axin and promotes Axin degradation via the proteasome pathway. K-756 binds to the induced pocket of TNKS and inhibits its enzyme activity. Moreover, PARP family enzyme assays showed that K-756 is a selective TNKS inhibitor. K-756 inhibited the cell growth of APC-mutant colorectal cancer COLO 320DM and SW403 cells by inhibiting the Wnt/beta-catenin pathway. An in vivo study showed that the oral administration of K-756 inhibited the Wnt/beta-catenin pathway in colon cancer xenografts in mice. To further explore the therapeutic potential of K-756, we also evaluated the effects of K-756 in non-small cell lung cancer cells. Although a single treatment of K-756 did not induce antiproliferative activity, when K-756 was combined with an EGFR inhibitor (gefitinib), it showed a strong synergistic effect. Therefore, K-756, a novel selective TNKS inhibitor, could be a leading compound in the development of anticancer agents. Mol Cancer Ther; 15(7); 1-10. (c)2016 AACR.
-
-	The Discovery and Characterization of K-756, a Novel Wnt/beta-Catenin Pathway Inhibitor Targeting Tankyrase.,Okada-Iwasaki R, Takahashi Y, Watanabe Y, Ishida H, Saito JI, Nakai R, Asai A Mol Cancer Ther. 2016 Apr 25. PMID:27196752<ref>PMID:27196752</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5ety" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:23, 12 July 2023

2023-07-12T08:23:44Z

←Older revision		Revision as of 08:23, 12 July 2023
Line 3:		Line 3:
	<StructureSection load='5ety' size='340' side='right'caption='[[5ety]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='5ety' size='340' side='right'caption='[[5ety]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ety]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ETY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ety]] is a 4 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=5ETY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ETY FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=K56:3~~-[[~~1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL~~]~~METHYL~~]~~-1,4-DIHYDROQUINAZOLIN-~~2~~-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.9Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/NAD~~(~~+)_ADP~~-~~ribosyltransferase NAD(+~~) ~~ADP~~-~~ribosyltransferase~~], ~~with EC number [http://www.brenda~~-~~enzymes.info~~/~~php/result_flat.php4?ecno~~=~~2.4.2.30 2.4.2.30]~~ </~~span~~></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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [https://pdbe.org/5ety PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [https://www.ebi.ac.uk/pdbsum/5ety PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ety ProSAT]</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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [~~http~~://pdbe.org/5ety PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ety PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ety ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>	+	[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_HUMAN] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Miyagi, H]]	+	[[Category: Miyagi H]]
-	[[Category: Saito, J]]	+	[[Category: Saito J]]
-	[[Category: Suzuki, M]]	+	[[Category: Suzuki M]]
-	[[Category: Takahashi, Y]]	+	[[Category: Takahashi Y]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Non-competitive]]~~	+
-	~~[[Category: Tankyrase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Wnt signal~~]]	+

OCA at 07:14, 19 February 2020

2020-02-19T07:14:15Z

←Older revision		Revision as of 07:14, 19 February 2020
Line 1:		Line 1:

	==Crystal Structure of human Tankyrase-1 bound to K-756==		==Crystal Structure of human Tankyrase-1 bound to K-756==
-	<StructureSection load='5ety' size='340' side='right' caption='[[5ety]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='5ety' size='340' side='right'caption='[[5ety]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ety]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ETY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ety]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ETY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [http://pdbe.org/5ety PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [http://www.ebi.ac.uk/pdbsum/5ety PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ety ProSAT]</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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [http://pdbe.org/5ety PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [http://www.ebi.ac.uk/pdbsum/5ety PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ety ProSAT]</span></td></tr>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5ety" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ety" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Miyagi, H]]		[[Category: Miyagi, H]]
	[[Category: Saito, J]]		[[Category: Saito, J]]

OCA at 02:25, 13 July 2016

2016-07-13T02:25:11Z

←Older revision		Revision as of 02:25, 13 July 2016
Line 6:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [http://pdbe.org/5ety PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [http://www.ebi.ac.uk/pdbsum/5ety 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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [http://pdbe.org/5ety PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [http://www.ebi.ac.uk/pdbsum/5ety PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ety ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 23:08, 23 June 2016

2016-06-23T23:08:27Z

←Older revision		Revision as of 23:08, 23 June 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ety is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of human Tankyrase-1 bound to K-756==
		+	<StructureSection load='5ety' size='340' side='right' caption='[[5ety]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ety]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ETY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ETY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K56:3-[[1-(6,7-DIMETHOXYQUINAZOLIN-4-YL)PIPERIDIN-4-YL]METHYL]-1,4-DIHYDROQUINAZOLIN-2-ONE'>K56</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=5ety FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ety OCA], [http://pdbe.org/5ety PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ety RCSB], [http://www.ebi.ac.uk/pdbsum/5ety PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Wnt/beta-catenin pathway is a well-known oncogenic pathway. Its suppression has long been considered as an important challenge in treating cancer patients. Among colon cancer patients in particular, most patients carry an adenomatous polyposis coli (APC) mutation that leads to an aberration of Wnt/beta-catenin pathway. To discover the small molecule inhibitors of the Wnt/beta-catenin pathway, we conducted high-throughput screening in APC-mutant colon cancer DLD-1 cells using a transcriptional reporter assay, which identified a selective Wnt/beta-catenin pathway inhibitor, K-756. K-756 stabilizes Axin and reduces active beta-catenin, and inhibits the genes downstream of endogenous Wnt/beta-catenin. We subsequently identified that K-756 is a tankyrase (TNKS) inhibitor. TNKS, which belongs to the PARP family, poly-ADP ribosylates Axin and promotes Axin degradation via the proteasome pathway. K-756 binds to the induced pocket of TNKS and inhibits its enzyme activity. Moreover, PARP family enzyme assays showed that K-756 is a selective TNKS inhibitor. K-756 inhibited the cell growth of APC-mutant colorectal cancer COLO 320DM and SW403 cells by inhibiting the Wnt/beta-catenin pathway. An in vivo study showed that the oral administration of K-756 inhibited the Wnt/beta-catenin pathway in colon cancer xenografts in mice. To further explore the therapeutic potential of K-756, we also evaluated the effects of K-756 in non-small cell lung cancer cells. Although a single treatment of K-756 did not induce antiproliferative activity, when K-756 was combined with an EGFR inhibitor (gefitinib), it showed a strong synergistic effect. Therefore, K-756, a novel selective TNKS inhibitor, could be a leading compound in the development of anticancer agents. Mol Cancer Ther; 15(7); 1-10. (c)2016 AACR.

-	~~Authors: Takahashi~~, Y., ~~Miyagi~~, H., ~~Suzuki~~, M., Saito, J.	+	The Discovery and Characterization of K-756, a Novel Wnt/beta-Catenin Pathway Inhibitor Targeting Tankyrase.,Okada-Iwasaki R, Takahashi Y, Watanabe Y, Ishida H, Saito JI, Nakai R, Asai A Mol Cancer Ther. 2016 Apr 25. PMID:27196752<ref>PMID:27196752</ref>

-	~~Description: Crystal Structure~~ of ~~human Tankyrase~~-~~1 bound to K~~-~~756~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5ety" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Miyagi, H]]		[[Category: Miyagi, H]]
-	[[Category: Suzuki, M]]
	[[Category: Saito, J]]		[[Category: Saito, J]]
		+	[[Category: Suzuki, M]]
	[[Category: Takahashi, Y]]		[[Category: Takahashi, Y]]
		+	[[Category: Inhibitor]]
		+	[[Category: Non-competitive]]
		+	[[Category: Tankyrase]]
		+	[[Category: Transferase]]
		+	[[Category: Wnt signal]]

OCA at 15:00, 2 December 2015

2015-12-02T15:00:32Z

←Older revision		Revision as of 15:00, 2 December 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ety is ON HOLD	+	The entry 5ety is ON HOLD until Paper Publication

	Authors: Takahashi, Y., Miyagi, H., Suzuki, M., Saito, J.		Authors: Takahashi, Y., Miyagi, H., Suzuki, M., Saito, J.

OCA: Protected "5ety" [edit=sysop:move=sysop]

2015-12-01T03:21:51Z

Protected "5ety" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:21, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5ety is ON HOLD Authors: Takahashi, Y., Miyagi, H., Suzuki, M., Saito, J. Description: Crystal Structure of human Tankyrase-1 bound to K-756 [[Cate...

2015-12-01T03:21:50Z

New page: '''Unreleased structure''' The entry 5ety is ON HOLD Authors: Takahashi, Y., Miyagi, H., Suzuki, M., Saito, J. Description: Crystal Structure of human Tankyrase-1 bound to K-756 [[Cate...

New page

'''Unreleased structure'''

The entry 5ety is ON HOLD

Authors: Takahashi, Y., Miyagi, H., Suzuki, M., Saito, J.

Description: Crystal Structure of human Tankyrase-1 bound to K-756
[[Category: Unreleased Structures]]
[[Category: Miyagi, H]]
[[Category: Suzuki, M]]
[[Category: Saito, J]]
[[Category: Takahashi, Y]]