USP7 deubiquitinates MDM2

Stable Identifier
R-HSA-3215295
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
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USP7 deubiquitinates MDM2
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In the presence of DAXX, USP7 deubiquitinates MDM2. DAXX expression therefore prolongs MDM2 half-life and inhibits TP53 activation (Tang et al. 2006). In the absence of DAXX or when DNA damage response is activated (Tang et al. 2006), USP7 associates with ubiquitinated TP53 rather than ubiquitinated MDM2 (Li et al. 2004, Sheng et al. 2006, Hu et al. 2006). USP7 also deubiquitinates MDM4 (MDMX) (Meulmeester et al. 2005, Sarkari et al. 2010). The role of DAXX in deubiquitination of MDM4 has not been examined.

Literature References
PubMed ID Title Journal Year
16474402 Molecular recognition of p53 and MDM2 by USP7/HAUSP

Sheng, Y, Saridakis, V, Sarkari, F, Duan, S, Wu, T, Arrowsmith, CH, Frappier, L

Nat. Struct. Mol. Biol. 2006
16402859 Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway

Hu, M, Gu, L, Li, M, Jeffrey, PD, Gu, W, Shi, Y

PLoS Biol. 2006
15053880 A dynamic role of HAUSP in the p53-Mdm2 pathway

Li, M, Brooks, CL, Kon, N, Gu, W

Mol. Cell 2004
16845383 Critical role for Daxx in regulating Mdm2

Tang, J, Qu, LK, Zhang, J, Wang, W, Michaelson, JS, Degenhardt, YY, El-Deiry, WS, Yang, X

Nat. Cell Biol. 2006
15916963 Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2

Meulmeester, E, Maurice, MM, Boutell, C, Teunisse, AF, Ovaa, H, Abraham, TE, Dirks, RW, Jochemsen, AG

Mol. Cell 2005
20713061 Further insight into substrate recognition by USP7: structural and biochemical analysis of the HdmX and Hdm2 interactions with USP7

Sarkari, F, La Delfa, A, Arrowsmith, CH, Frappier, L, Sheng, Y, Saridakis, V

J. Mol. Biol. 2010
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
thiol-dependent ubiquitin-specific protease activity of DAXX:(PolyUb,p-S166,S188-MDM2):USP7 [nucleoplasm]
Physical Entity
DAXX:(PolyUb,p-S166,S188-MDM2):USP7 [nucleoplasm]
Activity
thiol-dependent ubiquitin-specific protease activity (0004843)
Orthologous Events
USP7 deubiquitinates MDM2 (Bos taurus)
USP7 deubiquitinates MDM2 (Canis familiaris)
USP7 deubiquitinates MDM2 (Danio rerio)
USP7 deubiquitinates MDM2 (Drosophila melanogaster)
USP7 deubiquitinates MDM2 (Mus musculus)
USP7 deubiquitinates MDM2 (Rattus norvegicus)
USP7 deubiquitinates MDM2 (Sus scrofa)
USP7 deubiquitinates MDM2 (Xenopus tropicalis)
Authored
Orlic-Milacic, M  (2015-10-14)
Reviewed
Zaccara, S  (2016-02-04)
Inga, A  (2016-02-04)
Created
Orlic-Milacic, M  (2013-03-15)