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Ubiquitination is one of the most important post-translational modifications (PTMs) responsible for regulating the stability and activity of modified proteins. Deubiquitinating enzymes (DUBs) are proteases that reverse protein ubiquitination, a process important for normal homeostasis. DUBs have been noted to be associated with many human diseases, particularly cancer and neurological disorders. DUBs can influence carcinogenesis through multiple cellular pathways. Therefore, DUBs may become valuable therapeutic targets in oncology.
Our DUB Stable Cell Lines
Transfected stable cell lines are important research tools for drug discovery, compound screening, and gene therapy research. Creative Biogene has proven its success in the generation and validation of stable cell lines to accelerate your novel drug discoveries and biomedical research. We have generated a unique collection of DUB stable cell lines to provide powerful assay platforms for all research projects.
Key Features of Our DUB Stable Cell Lines
Humans encode approximately 100 different DUBs that regulate ubiquitin signaling by removing ubiquitin, thereby breaking down the chain and its signal while recycling ubiquitin for further conjugation. DUBs regulate diverse cellular functions, including proteasome-dependent and lysosome-dependent proteolysis, gene expression, DNA repair, cell cycle progression, apoptosis, localization, chromosome segregation, kinase activation, stemness maintenance, spermatogenesis, and degradation of signaling intermediates. Moreover, specific deubiquitinating enzymes are associated with the development of various diseases, including cancer, neurodegenerative disorders, and immune disorders.
Figure 1. Cycle of ubiquitin signaling. (Snyder N A, Silva G M. 2021)
DUB stable cell lines have become a valuable tool in the field of molecular biology and cancer research. These cell lines, designed to express a specific DUB enzyme at a stable and controlled level, allow scientists to study the role of DUBs in various cellular processes and disease conditions.
Applications for DUB stable cell lines include:
Case Study 1
Ubiquitin-specific peptidase 19 (USP19) is a member of the USP family and plays multiple roles in various biological processes such as cell differentiation, cell cycle progression, and apoptosis. Knowledge about the role and impact of USP19 in cancer, specifically clear cell renal cell carcinoma (ccRCC), is limited. The researchers evaluated the effect of USP19 on cell migration using Transwell and wound healing assays. These data indicate that USP19 inhibits ccRCC cell migration in vitro.
Figure 2. USP19 inhibits clear cell renal cell carcinoma cell migration in vitro. The migration ability of (A) USP19 overexpressing and (B) knockdown Caki-1 cells was determined by Transwell assay. The migration ability of (C) USP19 overexpressing and (D) knockdown Caki-1 cells was determined by wound healing assay. Reverse transcription-quantitative PCR analysis of MMP2 and MMP9 mRNA levels in (E) USP19 overexpressing or (F) knockdown Caki-1 cells. (G) Protein expression of MMP2 and MMP9 in USP19 overexpression or (H) knockdown Caki-1 cells. (Hu W, et al., 2020)
Case Study 2
Although gastric cancer (GC) is one of the most common cancers, understanding of its development and carcinogenesis is limited. Here, researchers explore the role of ubiquitin-specific protease 3 (USP3) in gastric cancer development and prognosis. Based on the expression level of USP3, HGC-27 GC cells with high USP3 levels were selected to help researchers elucidate the role of endogenous USP3 in the regulation of cell proliferation. Ubiquitin-specific protease 3-overexpressing SK-GT-2 cells were used to validate the results with HGC-27 cells. Elevated expression of cyclins D and E was observed in USP3-overexpressing SK-GT-2 cells. As can be seen from the results for HGC-27 cells, there was a slight increase in the expression of cyclin A and cyclin B. Furthermore, the amounts of cyclin-dependent kinases CDK1 and CDK2 were also slightly increased in SK-GT-2 cells overexpressing USP3. These data also suggest that USP3 plays an important role in cell cycle progression.
Figure 3. Validation of USP3 operation in HGC-27 and SK-GT-2 cells, and the effects of stable USP3 operation on cell growth, cell cycle distribution, and expression of cell cycle control molecules in cells. (Robinett R A, et al., 2018)
Q: What are deubiquitinating enzymes?
A: Deubiquitinating enzymes (DUBs) are a group of proteases that cleave the ubiquitin chains from target proteins, thereby facilitating their removal from degradation sites. These enzymes play a crucial role in the regulation of protein stability, localization, and activity.
Q: How do small molecule DUB inhibitors work?
A: In general, DUB inhibition leads to impaired proteasome function and accumulation of misfolded functional proteins, leading to cytotoxicity and death. DUBs that control oncogenic proteins can be targeted by UPS degradation of small molecules that inhibit deubiquitination activity, whereas DUBs that control tumor suppressor proteins can be targeted by increasing deubiquitination activity, thereby inhibiting oncogenic progression.
Q: How many DUB inhibitors have been discovered so far?
A: So far, more than 50 DUB inhibitors have been discovered, several of which are in preclinical development.
Q: How do DUB stable cell lines contribute to drug discovery and development?
A: High-throughput screening assays can be performed using these cell lines to identify small molecules or compounds that modulate DUB activity. This approach could identify new drug candidates capable of selectively inhibiting or activating specific DUB enzymes, which may have potential therapeutic applications. In fact, several compounds targeting DUB enzymes are currently being studied as anticancer drugs.
Q: How do researchers utilize DUB stable cell lines to investigate protein degradation pathways?
A: By manipulating the expression levels of specific DUB enzymes in these cell lines, researchers can study the effects on protein turnover and identify substrates for these enzymes. This information is critical for understanding the molecular mechanisms of diseases such as cancer, neurodegenerative diseases, and autoimmune diseases.
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