Reactome | USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN

USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN

Stable Identifier

R-HSA-5689950

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN

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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
16964248	FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP Maurice, MM, de Vries-Smits, AM, van der Horst, A, van den Broek, N, Burgering, BM, van Triest, MH, Colland, F, Brenkman, AB	Nat. Cell Biol.	2006
11923872	Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization Gu, W, Luo, J, Nikolaev, AY, Shiloh, A, Chen, D, Qin, J, Li, M	Nature	2002
15053880	A dynamic role of HAUSP in the p53-Mdm2 pathway Gu, W, Brooks, CL, Kon, N, Li, M	Mol. Cell	2004
15916963	Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2 Maurice, MM, Dirks, RW, Jochemsen, AG, Abraham, TE, Ovaa, H, Meulmeester, E, Teunisse, AF, Boutell, C	Mol. Cell	2005