8p14 - Revision history

OCA at 06:26, 4 December 2024

2024-12-04T06:26:24Z

← Older revision		Revision as of 06:26, 4 December 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/UBP28_HUMAN UBP28_HUMAN] Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus.<ref>PMID:16901786</ref> <ref>PMID:17558397</ref> <ref>PMID:17873522</ref> <ref>PMID:18662541</ref>		[https://www.uniprot.org/uniprot/UBP28_HUMAN UBP28_HUMAN] Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus.<ref>PMID:16901786</ref> <ref>PMID:17558397</ref> <ref>PMID:17873522</ref> <ref>PMID:18662541</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The development of cancer therapeutics is often hindered by the fact that specific oncogenes cannot be directly pharmaceutically addressed. Targeting deubiquitylases that stabilize these oncogenes provides a promising alternative. USP28 and USP25 have been identified as such target deubiquitylases, and several small-molecule inhibitors indiscriminately inhibiting both enzymes have been developed. To obtain insights into their mode of inhibition, we structurally and functionally characterized USP28 in the presence of the three different inhibitors AZ1, Vismodegib and FT206. The compounds bind into a common pocket acting as a molecular sink. Our analysis provides an explanation why the two enzymes are inhibited with similar potency while other deubiquitylases are not affected. Furthermore, a key glutamate residue at position 366/373 in USP28/USP25 plays a central structural role for pocket stability and thereby for inhibition and activity. Obstructing the inhibitor-binding pocket by mutation of this glutamate may provide a tool to accelerate future drug development efforts for selective inhibitors of either USP28 or USP25 targeting distinct binding pockets.

			Structural basis for the bi-specificity of USP25 and USP28 inhibitors.,Patzke JV, Sauer F, Nair RK, Endres E, Proschak E, Hernandez-Olmos V, Sotriffer C, Kisker C EMBO Rep. 2024 Jul;25(7):2950-2973. doi: 10.1038/s44319-024-00167-w. Epub 2024 , May 30. PMID:38816515<ref>PMID:38816515</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8p14" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:03, 22 May 2024

2024-05-22T08:03:13Z

← Older revision		Revision as of 08:03, 22 May 2024
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8p14 is ~~ON HOLD until 2025~~-05-11		==USP28 USP domain in complex with Vismodegib==
			<StructureSection load='8p14' size='340' side='right'caption='[[8p14]], [[Resolution\|resolution]] 2.57Å' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>[[8p14]] is a 1 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=8P14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P14 FirstGlance]. <br>
	~~Description~~:		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.57Å</td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VIS:2-CHLORANYL-~{N}-(4-CHLORANYL-3-PYRIDIN-2-YL-PHENYL)-4-METHYLSULFONYL-BENZAMIDE'>VIS</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=8p14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p14 OCA], [https://pdbe.org/8p14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p14 RCSB], [https://www.ebi.ac.uk/pdbsum/8p14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p14 ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/UBP28_HUMAN UBP28_HUMAN] Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus.<ref>PMID:16901786</ref> <ref>PMID:17558397</ref> <ref>PMID:17873522</ref> <ref>PMID:18662541</ref>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Karal Nair R]]
			[[Category: Kisker C]]
			[[Category: Sauer F]]

OCA at 02:36, 25 May 2023

2023-05-25T02:36:16Z

← Older revision		Revision as of 02:36, 25 May 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8p14 is ON HOLD		The entry 8p14 is ON HOLD until 2025-05-11

	Authors:		Authors:

OCA: Protected "8p14" [edit=sysop:move=sysop]

2023-05-18T05:46:03Z

Protected "8p14" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:46, 18 May 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8p14 is ON HOLD Authors: Description: Category: Unreleased Structures

2023-05-18T05:46:02Z

New page: '''Unreleased structure''' The entry 8p14 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8p14 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]