Background: USP7 (ubiquitin specific protease 7, also known as HAUSP) is one of the
deubiquitinating enzymes (DUB) that reverses ubiquitination and spares substrate proteins from
Methods: After a brief introduction of ubiquitin-proteasome system (UPS) and human DUB, this
review focuses on the structural and functional complexity of USP7 in tumor development and
progression. Afterwards, physiological regulatory mechanisms and manipulation strategies for
USP7 are elaborated. Finally, we discuss the advances and difficulties of USP7 as a novel therapeutic
target for cancer.
Results: It is mostly concerned that USP7 regulates the dynamics of the p53 and Mdm2 network
by deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Recently, USP7 has also been
recognized as a regulator of many other tumor associated proteins such as FOXO, PTEN and
Claspin, consequently being involved in cell cycle control, DNA damage response, apoptosis and
many other cellular processes. Consistently, aberrant USP7 expression and activity have been connected
to various types of cancers, which along with lots of validating genetic and functional experiments
make this enzyme a compelling target for the treatment of cancer. Currently disclosed
inhibitor discovery programs and relevant research have identified several synthetic small molecules,
natural compounds, small peptides and one ubiquitin variant that have specific USP7 inhibitory
effects and considerable antitumor activities.
Conclusion: Taken together, USP7 is a promising therapeutic target and USP7 inhibitors hold
promise as a new approach to cancer therapy.