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The Multifaceted Roles of USP7: New Therapeutic Opportunities

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Abstract

The deubiquitylating enzyme USP7 (HAUSP) sits at a critical node regulating the activities of numerous proteins broadly characterized as tumor suppressors, DNA repair proteins, immune responders, viral proteins, and epigenetic modulators. Aberrant USP7 activity may promote oncogenesis and viral disease making it a compelling target for therapeutic intervention. Disclosed drug discovery programs have identified inhibitors of USP7 such as P005091 with cellular proof of concept and anti-proliferative activity in cancer models. Taken together, USP7 inhibitors hold promise as a new strategy for the treatment of disease.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

ATR:

Ataxia telangiectasia and Rad3-related protein

DAXX:

Death domain associated protein

DUB:

Deubiquitylating enzyme

EBNA1:

Epstein-Barr nuclear antigen 1

EBV:

Epstein-Barr virus

EGF:

Epidermal growth factor

FOXO:

Forkhead box O

GMPS:

Guanosine monophosphate synthase

HDAC:

Histone deacetylase

HDM2:

Human double minute 2

HDMX:

Human double minute 4

HSV:

Herpes simplex virus

ICP0:

Infected cell protein 0

PI3K:

Phosphatidylinositol-3-kinase

PML:

Promyelocytic leukemia protein

Pc:

Polycomb

PRC1:

Polycomb repressive complex 1

PTEN:

Phosphatase and tensin homologue

TLR:

Toll-like receptor

TRAF:

Tumor necrosis factor-receptor associated factor

USP7:

Ubiquitin specific peptidase 7

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Acknowledgments

We wish to thank our collaborators and our colleagues at Progenra for their many insightful comments on the roles of USP7 in disease. This study was supported in part by NIH grants CA115205 and DK071391.

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  1. Progenra Inc, 277 Great Valley Parkway, Malvern, PA, 19355, USA

    Benjamin Nicholson & K. G. Suresh Kumar

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Correspondence to Benjamin Nicholson.

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Nicholson, B., Suresh Kumar, K.G. The Multifaceted Roles of USP7: New Therapeutic Opportunities. Cell Biochem Biophys 60, 61–68 (2011). https://doi.org/10.1007/s12013-011-9185-5

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