The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics

Li, Qiong; Ye, Chanqi; Tian, Tian; Jiang, Qi; Zhao, Peng; Wang, Xiaoting; Liu, Feiye; Shan, Jianzhen; Ruan, Jian

doi:10.1038/s41419-022-04853-2

Cited by 17 publications

(18 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finger sub-domain interacts with the ubiquitin substrate, and the palm, thumb, and active site resemble the catalytic triads as found there ( Hu et al., 2002 ). A catalytic domain with accessory domains is frequently seen in DUBs, some of which aid in target detection ( Kim et al., 2016 ).USPs are the largest amongst all DUBs subfamily that contributes to the development of various malignancies ( Clague et al., 2019 ; Li et al., 2022 ). Therefore, more research using these DUBs as a therapeutic target is necessary.…”

Section: Functional Role Of Important Dub Domains In Humanmentioning

confidence: 99%

“…Recent research has shown that the USP20 domain plays a crucial role in the carcinogenesis of several cancer types, including adult T-cell leukemia, breast cancer, colon cancer, lung cancer, and gastric cancer. Consequently, modulating USP20 activity can be of unique cancer therapy ( Li et al., 2022 ).…”

Section: Functional Role Of Important Dub Domains In Humanmentioning

confidence: 99%

See 1 more Smart Citation

The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review

Kumar

Mandal

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.

show abstract

Section: Functional Role Of Important Dub Domains In Humanmentioning

confidence: 99%

Section: Functional Role Of Important Dub Domains In Humanmentioning

confidence: 99%

The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review

Kumar

Mandal

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…USP20 promotes the tumorigenesis of several cancer types, such as breast and cervical cancer; however, it exhibits inhibitory effects on GC [ 16 ]. Past reports have indicated that USP20 overexpression inhibited cell proliferation and delayed the cell cycle transition from the G1 to S phase by stabilizing Claspin [ 43 , 170 ].…”

Section: Usps and Gcmentioning

confidence: 99%

“…Hence, DUBs have attracted attention as therapeutic targets, and DUB inhibitors have been developed, with some now in preclinical development or clinical trials [ 15 ]. To date, approximately 100 DUBs have been reported and are classified into seven subfamilies based on their sequence and structural similarities as follows: ubiquitin-specific proteases (USPs), ubiquitin carboxy-terminal hydrolases (UCHs), ovarian tumor proteases (OTUs), Jab1/MPN domain-associated metalloenzymes (JAMMs), Machado–Joseph disease proteases (MJDs), the monocyte chemotactic protein-induced protease family (MINDYs), and Zn-finger and UFSP domain proteins (ZUFSPs) ( Figure 1 ) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Research Progress for Targeting Deubiquitinases in Gastric Cancers

Gong

et al. 2022

Cancers

View full text Add to dashboard Cite

Gastric cancers (GCs) are malignant tumors with a high incidence that threaten global public health. Despite advances in GC diagnosis and treatment, the prognosis remains poor. Therefore, the mechanisms underlying GC progression need to be identified to develop prognostic biomarkers and therapeutic targets. Ubiquitination, a post-translational modification that regulates the stability, activity, localization, and interactions of target proteins, can be reversed by deubiquitinases (DUBs), which can remove ubiquitin monomers or polymers from modified proteins. The dysfunction of DUBs has been closely linked to tumorigenesis in various cancer types, and targeting certain DUBs may provide a potential option for cancer therapy. Multiple DUBs have been demonstrated to function as oncogenes or tumor suppressors in GC. In this review, we summarize the DUBs involved in GC and their associated upstream regulation and downstream mechanisms and present the benefits of targeting DUBs for GC treatment, which could provide new insights for GC diagnosis and therapy.

show abstract

“…Deubiquitinases (DUB) in the deubiquitination process remove ubiquitin chains to preserve the labeled substrate proteins (12). Ubiquitin-specific peptidase 20 (USP20) is a pivotal member of the DUB family and regulates the stability of multiple proteins via the ubiquitin-proteasome pathway (13,14). USP20 is also associated with multiple biological processes (15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice

Zhang

Shi²,

Li³

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionObesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive.MethodsWe performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG.ResultsCompared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro. Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro. Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway.ConclusionThe downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.

show abstract

The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics

Cited by 17 publications

References 136 publications

The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review

The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review

Research Progress for Targeting Deubiquitinases in Gastric Cancers

Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice

Contact Info

Product

Resources

About