USP14 Gene Editing    

The ubiquitin-proteasome system is the main pathway of non-lysosomal intracellular protein degradation, playing an important role in various cellular responses including cell division, proliferation, and apoptosis. More than 80 % of all cellular proteins are processed by this system. This fundamental role for the proteasome singles it out as a unique target for anticancer therapy. Ubiquitin-specific protease 14 (USP14), a member of the ubiquitin-specific processing (UBP) family of proteases, is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin part from ubiquitin-fused precursors and ubiquitinylated proteins. USP14 negatively regulates proteasome activity through ubiquitin chain disassembly as well as by a noncatalytic mechanism. USP14 inhibitors produce selective effects on the turnover of proteasome substrates, indicating that the rate at which USP14 disassembles proteasome-bound ubiquitin chains may depend on the nature of the substrate.

USP14 and Cancer

It was found that the USP14 expression was associated with leukemic, intrahepatic cholangiocarcinoma, colorectal cancer, and lung carcinoma. USP14 is upregulated in lung cancer and that it could be inhibited by IU1-47, an USP14 inhibitor. Importantly, USP14 is not involved in apoptosis, but it is involved in autophagy. These findings show that USP14 is a promising target in lung cancer therapy. In endometrial cancer cells, USP14 is expressed along with the marker of proliferation Ki67 in situ. Pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, reduces the cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis. In addition, it was detected that USP14 was over-expressed in the ovarian serous cystadenocarcinoma compared with adjacent normal tissues by PCR and immunohistochemical staining. Immunohistochemistry analysis was performed on formalin-fixed paraffin-embedded section of 116 cases of epithelial ovarian cancer (EOCs) and suggested that USP14 was significantly associated with clinical pathologic variables.

USP14 Inhibitors as Potential Anticancer Agents

Since the discovery of ubiquitination and acknowledgement of its key role in maintaining cellular homeostasis, the interest in exploring this posttranslational-protein modification for the treatment of various diseases is evergrowing. Different methods are being pursued to harness the ubiquitin (Ub) system, including inhibition of DUBs. USP14 was shown to be involved in the regulation of multiple cellular processes, not only by controlling protein stability but also by modulating signal transduction via nondegradative mechanisms. Since USP14 is related to the clearance of protein aggregates and found to be overexpressed in tumors, it has been considered an interesting therapeutic target for the treatment of neurodegenerative disorders and cancer. So far, two different types of USP14 inhibitors have been published; the dual USP14/UCHL5 inhibitors and the selective USP14 inhibitors.

USP14 Gene Editing Services

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively USP14 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• USP14 Gene Knockout: We offer USP14 gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• USP14 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop USP14 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of USP14 knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

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