About: USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin

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About: USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)- mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Effi cient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCF TrCP - dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specifi c protease 7 (USP7) as a novel reg ulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we fi nd that in addition to the M phase ? specifi c, SCF TrCP -mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifi cally opposes the Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)- mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Effi cient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCF TrCP - dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specifi c protease 7 (USP7) as a novel reg ulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we fi nd that in addition to the M phase ? specifi c, SCF TrCP -mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifi cally opposes the (en)
Title	USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin (en)
skos:prefLabel	USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin (en)
skos:notation	RIV/61989592:15110/09:00010975!RIV10-MSM-15110___
http://linked.open...avai/riv/aktivita	Z
http://linked.open...avai/riv/aktivity	Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika	1
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Bártek, Jiří
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	348066
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/09:00010975
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	DNA damage response; Chk1 signaling; ubiquitin-specific protease; genotoxic stress (en)
http://linked.open.../riv/klicoveSlovo	Chk1 signaling ubiquitin-specific protease DNA damage response genotoxic stress
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[A51F72A18FC2]
http://linked.open...i/riv/nazevZdroje	Journal of Cell Biology
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	5 (xsd:int)
http://linked.open...UplatneniVysledku	2009
http://linked.open...v/svazekPeriodika	184
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Lukáš, Jiří Bekker-Jensen, Simon Faustrup, Helene Mailand, Niels
http://linked.open...n/vavai/riv/zamer	Modulation of signalling and regulatory pathways in normal and cancer cells
issn	0021-9525
number of pages	17 (xsd:int)
http://localhost/t...ganizacniJednotka	15110
is http://linked.open...avai/riv/vysledek of	USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin

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