USP7 Inhibitors Reveal a Differentiated Mechanism of p53-Driven Anti-Cancer Activity

Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that cleaves ubiquitin from a range of substrates, shielding them from degradation by the proteasome. USP7 activity has been implicated in cancer progression and its overexpression is associated with tumor aggressiveness and poor prognosis in a variety of cancer types, making USP7 inhibition an attractive strategy for the treatment of cancer.  MDM2 is an E3 ubiquitin ligase that ubiquitinates the p53 tumor suppressor, marking it for degradation by the proteasome. USP7 deubiquitinates and stabilizes MDM2, which promotes degradation of p53.

WuXi AppTec scientists contributed to a study illustrating the mechanistic differences between USP7 and MDM2 inhibitors and their effects on p53 signaling. This work highlights the therapeutic potential of USP7 inhibitors and reveals specific opportunities for their use in the treatment of acute myeloid leukemia (AML).