USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN

Stable Identifier
R-HSA-5689950
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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USP7 (HAUSP) is able to deubiquitinate many substrates. It is a key regulator of the tumor suppressor TP53 (p53) (Vousden & Lu 2002). It can act on TP53 directly, or indirectly by acting on the E3 ligase MDM2, which can ubiquitinate TP53 (Chene 2003, Li et al. 2002, 2004, Kon et al. 2010). USP7 also regulates MDM4 (Mdmx), a structural homolog of MDM2 (Meulmeester et al. 2005, Chen 2012). USP7 interacts with and deubiquitinates FOXO4 in response to oxidative stress (van der Horst et al. 2006) and reduces monoubiquitinylation of PTEN, presumably on the previously identified lysine residues 13 and 289 (Trotman et al. 2007), reducing nuclear PTEN levels (Song et al. 2008).

Literature References
PubMed ID Title Journal Year
11923872 Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization

Li, M, Chen, D, Shiloh, A, Luo, J, Nikolaev, AY, Qin, J, Gu, W

Nature 2002
16964248 FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP

van der Horst, A, de Vries-Smits, AM, Brenkman, AB, van Triest, MH, van den Broek, N, Colland, F, Maurice, MM, Burgering, BM

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

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

Mol. Cell 2004
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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
thiol-dependent ubiquitinyl hydrolase activity of USP7:PolyUb-TP53,PolyUb-MDM2,PolyUb-MDM4,PolyUb-FOXO4,PolyUb-PTEN [nucleoplasm]
Physical Entity
Activity
Orthologous Events
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Created