Nuclear deubiquitination in the spotlight: the multifaceted nature of USP7 biology in disease

Radhika Rawat; Daniel T. Starczynowski; Panagiotis Ntziachristos

doi:10.1016/j.ceb.2019.02.008

Nuclear deubiquitination in the spotlight: the multifaceted nature of USP7 biology in disease

Radhika Rawat, Daniel T. Starczynowski, Panagiotis Ntziachristos

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Review article › peer-review

37 Scopus citations

Abstract

Ubiquitination is a versatile and tightly regulated post-translational protein modification with many distinct outcomes affecting protein stability, localization, interactions, and activity. Ubiquitin chain linkages anchored on substrates can be further modified by additional post-translational modifications, including phosphorylation and SUMOylation. Deubiquitinases (DUBs) reverse these ubiquitin marks with matched levels of precision. Over hundred known DUBs regulate a wide variety of cellular events. In this review, we focus on ubiquitin-specific protease 7 (USP7, also known as herpesvirus-associated ubiquitin-specific protease, or HAUSP) as one of the best studied, disease-associated DUBs. By highlighting the functions of USP7, particularly in the nucleus, and the emergence of the newest generation of USP7 inhibitors, we illustrate the importance of individual DUBs in the nucleus, and the therapeutic prospects of DUB targeting in human disease.

Original language	English (US)
Pages (from-to)	85-94
Number of pages	10
Journal	Current Opinion in Cell Biology
Volume	58
DOIs	https://doi.org/10.1016/j.ceb.2019.02.008
State	Published - Jun 2019

Funding

The authors have been supported by an NIHT32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI (R00CA188293), the National Science Foundation, the American Society of Hematology, the Leukemia Research Foundation, the St. Baldrick's Foundation, the H Foundation, the Gabrielle's Angel Foundation, The Hartwell Foundation, the Elsa U. Pardee Foundation, a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos). The authors have been supported by an NIH T32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI ( R00CA188293 ), the National Science Foundation , the American Society of Hematology , the Leukemia Research Foundation , the St. Baldrick’s Foundation , the H Foundation , the Gabrielle’s Angel Foundation , The Hartwell Foundation , the Elsa U. Pardee Foundation , a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos).

ASJC Scopus subject areas

Cell Biology

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10.1016/j.ceb.2019.02.008

Cite this

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title = "Nuclear deubiquitination in the spotlight: the multifaceted nature of USP7 biology in disease",

abstract = "Ubiquitination is a versatile and tightly regulated post-translational protein modification with many distinct outcomes affecting protein stability, localization, interactions, and activity. Ubiquitin chain linkages anchored on substrates can be further modified by additional post-translational modifications, including phosphorylation and SUMOylation. Deubiquitinases (DUBs) reverse these ubiquitin marks with matched levels of precision. Over hundred known DUBs regulate a wide variety of cellular events. In this review, we focus on ubiquitin-specific protease 7 (USP7, also known as herpesvirus-associated ubiquitin-specific protease, or HAUSP) as one of the best studied, disease-associated DUBs. By highlighting the functions of USP7, particularly in the nucleus, and the emergence of the newest generation of USP7 inhibitors, we illustrate the importance of individual DUBs in the nucleus, and the therapeutic prospects of DUB targeting in human disease.",

author = "Radhika Rawat and Starczynowski, {Daniel T.} and Panagiotis Ntziachristos",

note = "Funding Information: The authors have been supported by an NIHT32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI (R00CA188293), the National Science Foundation, the American Society of Hematology, the Leukemia Research Foundation, the St. Baldrick's Foundation, the H Foundation, the Gabrielle's Angel Foundation, The Hartwell Foundation, the Elsa U. Pardee Foundation, a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos). Funding Information: The authors have been supported by an NIH T32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI ( R00CA188293 ), the National Science Foundation , the American Society of Hematology , the Leukemia Research Foundation , the St. Baldrick{\textquoteright}s Foundation , the H Foundation , the Gabrielle{\textquoteright}s Angel Foundation , The Hartwell Foundation , the Elsa U. Pardee Foundation , a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos). Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

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N1 - Funding Information: The authors have been supported by an NIHT32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI (R00CA188293), the National Science Foundation, the American Society of Hematology, the Leukemia Research Foundation, the St. Baldrick's Foundation, the H Foundation, the Gabrielle's Angel Foundation, The Hartwell Foundation, the Elsa U. Pardee Foundation, a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos). Funding Information: The authors have been supported by an NIH T32 CA009560 Carcinogenesis Training Grant (to R. Rawat), and by NCI ( R00CA188293 ), the National Science Foundation , the American Society of Hematology , the Leukemia Research Foundation , the St. Baldrick’s Foundation , the H Foundation , the Gabrielle’s Angel Foundation , The Hartwell Foundation , the Elsa U. Pardee Foundation , a Gilead Research Scholarship and the Zell Foundation (to P. Ntziachristos). Publisher Copyright: © 2019 Elsevier Ltd

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Nuclear deubiquitination in the spotlight: the multifaceted nature of USP7 biology in disease

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