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Not all DUBs are equal

I guess, most researchers should upgrade their knowledge about MDM2----it ubiquitinates p53 (a tumor suppressor), and  Bortezomib now, itself is regulated (deubiquitination) by USP7 (ubiquitin specific protease 7,also called HAUSP, herpesvirus-associated ubiquitin-specific protease. As we know, herpesvirus is often oncogenic. USP7 is indeed a marker in some tumors. USP7 is ubiquitin specific, but not very protein-specific----p53, chk1,PTEN, claspin, FOXO4 are all its LY294002 substrate, making a complex situation. Small molecule interference such as P5091 is applied to USP7 and has indicated its role in DNA repair, immune reaction, and neuronal synapse. By targeting USP7, MDM2 is inhibited, allowing protected p53 to exert anti-tumor effect.
Domagoj Vucic et al has already explained the reason: USP7 binds to MDM2 (not phosphorylated MDM2) more tightly than p53. Anyway, USP7 is regarded as a drug target.
By the way, USP9X is another candidate because it associates with Bcl-2. More secrets are included in Benedikt M Kessler's Review: Selective and reversible inhibitors of ubiquitin-specific protease 7: a patent evaluation (WO2013030218)

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