Quantitative Deubiquitinase (DUB) Interactomics to Dissect the Biology of Cancer Associated DUBs
type: CreativeWork
description: Ubiquitination is a prominent reversible post-translational modification, which plays crucial roles in regulating numerous cellular events. Conversely, deubiquitination is the removal of ubiquitin/polyubiquitin chains from ubiquitinated proteins. Deubiquitination is carried out by the class of enzymes called deubiquitinases (DUBs). These DUBs have vital roles in the regulation of protein ubiquitination and have a profound influence on the fate of proteins and their activity. Dysregulation of DUBs has been associated with the development of many human diseases, including various cancers. Therefore, DUBs are increasingly becoming attractive therapeutic targets in recent years. For instance, the USP14 DUB inhibitor VLX1570 entered clinical trials (now suspended) for the treatment of multiple myeloma (Want et al., 2016). Though DUBs are implicated in cancers, the precise cellular roles of many DUBs remain poorly understood. USP35, a poorly studied DUB was identified with genomic amplification in breast and ovarian cancers (Boehringer Ingelheim, Vienna, Austria). Its amplification was correlated with overexpression and poor prognosis (Chin et al., 2007). siRNAs knockdown of USP35, in USP35 amplified cancer cells resulted in reduced cell proliferation. Therefore, USP35 was suggested to be an attractive therapeutic target for cancer treatment. During the start of my project, the biological function of USP35 was unknown. Therefore, in the present study, I explored the functions of USP35 with interaction proteomics, bioinformatics and cell biology-based approaches. Interaction proteomic analysis of USP35 with immunoprecipitation (IP) of endogenous USP35 yielded few USP35 interactors and many non-specific IgG-interacting proteins. Intriguingly, we found evidence for the existence of at least two major isoforms of USP35 with distinct N-termini. The canonical full-length USP35 (iso1) is the major isoform and a shorter isoform with an N-terminal deletion, USP35270-1018 (iso2) is…
abstract: Ubiquitination is a prominent reversible post-translational modification, which plays crucial roles in regulating numerous cellular events. Conversely, deubiquitination is the removal of ubiquitin/polyubiquitin chains from ubiquitinated proteins. Deubiquitination is carried out by the class of enzymes called deubiquitinases (DUBs). These DUBs have vital roles in the regulation of protein ubiquitination and have a profound influence on the fate of proteins and their activity. Dysregulation of DUBs has been associated with the development of many human diseases, including various cancers. Therefore, DUBs are increasingly becoming attractive therapeutic targets in recent years. For instance, the USP14 DUB inhibitor VLX1570 entered clinical trials (now suspended) for the treatment of multiple myeloma (Want et al., 2016). Though DUBs are implicated in cancers, the precise cellular roles of many DUBs remain poorly understood. USP35, a poorly studied DUB was identified with genomic amplification in breast and ovarian cancers (Boehringer Ingelheim, Vienna, Austria). Its amplification was correlated with overexpression and poor prognosis (Chin et al., 2007). siRNAs knockdown of USP35, in USP35 amplified cancer cells resulted in reduced cell proliferation. Therefore, USP35 was suggested to be an attractive therapeutic target for cancer treatment. During the start of my project, the biological function of USP35 was unknown. Therefore, in the present study, I explored the functions of USP35 with interaction proteomics, bioinformatics and cell biology-based approaches. Interaction proteomic analysis of USP35 with immunoprecipitation (IP) of endogenous USP35 yielded few USP35 interactors and many non-specific IgG-interacting proteins. Intriguingly, we found evidence for the existence of at least two major isoforms of USP35 with distinct N-termini. The canonical full-length USP35 (iso1) is the major isoform and a shorter isoform with an N-terminal deletion, USP35270-1018 (iso2) is…
author: Natarajan, Jayaprakash
language: eng
keywords: Proteomics, Bioinformatics, Deubiquitylating enzymes, Cell & molecular biology, Mass Spectrometry
date published: 2019
date modified: 2026-07-24T02:08:46Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee