title: The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics.
abstract: The addition of mono-ubiquitin or poly-ubiquitin chain to signaling proteins in response to DNA damage signal is thought to be a critical event that facilitates the recognition of DNA damage lesion site, the activation of checkpoint function, termination and checkpoint response and the recruitment of DNA repair proteins. Despite the ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in orchestrating DNA damage response as well as DNA repair processes. Deregulated ubiquitination and deubiquitination could lead to genome instability that in turn causes tumorigenesis. Recent TCGA study has further revealed the connection between mutations in alteration of DUBs and various types of tumors. In addition, emerging drug design based on DUBs provides a new avenue for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and specificity of DUBs, and highlight the recent discoveries of DUBs in the modulation of ubiquitin-mediated DNA damage response and DNA damage repair. We will furthermore discuss the DUBs involved in the tumorigenesis as well as interception of deubiquitination as a novel strategy for anti-cancer therapy.
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA ; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.
authors.forename: Haojing
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
keywords: Anti-cancer treatment; DNA damage repair; DNA damage response; Deubiquitinases; Tumorigenesis