Reactome | USP7 deubiquitinates MDM2

USP7 deubiquitinates MDM2

Stable Identifier

R-HSA-3215295

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - Regulation of TP53 Activity (Homo sapiens)
        
        Regulation of TP53 Expression and Degradation (Homo sapiens)
        
        Regulation of TP53 Degradation (Homo sapiens)
        
        USP7 deubiquitinates MDM2 (Homo sapiens)

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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
16402859	Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway Gu, L, Shi, Y, Gu, W, Jeffrey, PD, Hu, M, Li, M	PLoS Biol.	2006
16474402	Molecular recognition of p53 and MDM2 by USP7/HAUSP Arrowsmith, CH, Duan, S, Sheng, Y, Sarkari, F, Frappier, L, Wu, T, Saridakis, V	Nat. Struct. Mol. Biol.	2006
15053880	A dynamic role of HAUSP in the p53-Mdm2 pathway Gu, W, Brooks, CL, Kon, N, Li, M	Mol. Cell	2004
16845383	Critical role for Daxx in regulating Mdm2 Wang, W, Zhang, J, Degenhardt, YY, Tang, J, Qu, LK, Michaelson, JS, Yang, X, El-Deiry, WS	Nat. Cell Biol.	2006
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
20713061	Further insight into substrate recognition by USP7: structural and biochemical analysis of the HdmX and Hdm2 interactions with USP7 Arrowsmith, CH, Sheng, Y, Sarkari, F, La Delfa, A, Frappier, L, Saridakis, V	J. Mol. Biol.	2010