• Molecules and Cells
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• v.42 no.1
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• pp.17-27
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• 2019

Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.

• The Korean Journal of Zoology
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• v.38 no.2
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• pp.220-229
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• 1995

uftraspirocle (usa) gene product (Uspl is a member of the superfamilv of steroid hormone receptors in Drosophila melonogaster which mediate the hormone action by heteromerization with ecdvsone receptor (EcR). Based on the genetic and molecular characterization of usp, it has been proposed that Usp funtions in at least three significant developmental pathway: embrvogenesis, eve morphogenesis, and female reproduction. In this study, the expression patterns of Usp were investigated by immunohistochemistrv in individual tissues from diHernt developmental stases of Drosophila. Usp is localized in the nucleus with ubiquitous distribution throughout development. Usp expression is detected throughout embrvogenesis. Usp is expressed in imaginal and lanral tissues from late third instar 18nra. The expression pattern of Usp is overlapped by those of EcR. Also Usp is expressed in differentiating adult reproductive organs. This result suggests that Usp is not a transcriptional regulatory factor modulating hormonal response during development, but also play some roles in female and male reproduction of Drosophila.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.11.1-11.12
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• 2018

USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

• BMB Reports
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• v.56 no.8
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• pp.451-456
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• 2023

Deubiquitinases (DUBs) are an essential component of the ubiquitin-proteasome system (UPS). They trim ubiquitin from substrate proteins, thereby preventing them from degradation, and modulate different cellular processes. Ubiquitin-specific protease 14 (USP14) is a DUB that has mainly been studied for its role in tumorigenesis in several cancers. In the present study, we found that the protein levels of USP14 were remarkably higher in gastric cancer tissues than in the adjacent normal tissues. We also demonstrated that the inhibition of USP14 activity using IU1 (an USP14 inhibitor) or the inhibition of USP14 expression using USP14-specific siRNA markedly reduced the viability of gastric cancer cells and suppressed their migratory and invasive abilities. The reduction in gastric cancer cell proliferation due to the inhibition of USP14 activity was a result of the increase in the degree of apoptosis, as evidenced by the increased expression levels of cleaved caspase-3 and cleaved PARP. Furthermore, an experiment using the USP14 inhibitor IU1 revealed that the inhibition of USP14 activity suppressed 5-fluorouracil (5-FU) resistance in GC cells. Collectively, these findings indicate that USP14 plays critical roles in gastric cancer progression and suggest its potential to serve as a novel therapeutic target for gastric cancer treatment.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.4 no.1
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• pp.79-92
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• 1984

The analysis of total load was carried out by using the theory of unit stseam power (USP). The dimensionless USP equation of $S_R$ which was the rate of suspended load and bed load was derived from the USP function by applying the Einstein's reference concentration and Stokes' fall velocity. And the R relationship between the water discharge and Reynolds number (Re) was discussed, and it was shown that USP was closely related with Re. The value of $S_R$ was determined from the experimental data of Han River downstream and Mantz. And it was tested to several observatories of Korean Rivers. A good correlation among USP, suspended load and $S_R$ was shown and USP was increased with the increment of the turbulent intensity. Judging from the above results, it is considered this study can be contributed to estimate the total load.

• Journal of Animal Science and Technology
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• v.63 no.5
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• pp.977-983
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• 2021

Closely correlated expression patterns between ubiquitin specific peptidase 9X-linked (USP9X) and adherens junction formation factor (Afadin) in mouse testis development suggests that Usp9x regulates the deubiquitination of Af-6 (also known as Afadin, AFDN), and subsequently, the cell adhesion dynamics during gametogenesis. However, this relationship has not yet been tested in other domestic animals. The study was examined the temporal and spatial expression patterns of porcine USP9X and AFDN from the pre-pubertal to adult stages using real time-PCR and immunohistochemistry. Furthermore, we detected the transcripts of USP9X and AFDN in the testis of 1-, 6- and 12-months old boar, respectively. USP9X and AFDN were found to have similar expressions patterns, with basal expression after 1 month followed by a significant up-regulation from 6 months (puberty) onwards. In addition, neither the AFDN or USP9X proteins were detected in spermatogenic cells but they were expressed in the leydig cells and sertoli cells. USP9X was detected around the basal lamina during pre-puberty, and predominantly expressed in the leydig cells at puberty. Finally, in adult testis, USP9X was increased at the sertoli cell-cell interface and the sertoli cell-spermatid interface. In summary, closely correlated expression patterns between USP9X and AFDN in boar testis supports the previous findings in mice. Furthermore, the junction connections between the sertoli cells may be regulated by the ubiquitination process mediated via USP9X.

• Proceedings of the Korea Contents Association Conference
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• 2017.05a
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• pp.495-496
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• 2017

USP는 독특한 판매제안이란 의미로 제품 및 디자인의 차별화 혹은 브랜드 커뮤니케이션 수행의 차별화로 확장되어 이용되고 있다. 경쟁사에 대한 효과적이고 지속적인 경쟁우위를 유지하기 위한 마케팅 및 브랜드 커뮤니케이션 차별화 전략 중 USP 전략을 기술적 요인에 의한 제품차별화 및 브랜드, 광고, 유통 및 고객서비스 등과 같은 마케팅 활동에 의한 차별화로 인식하고 기업의 광고 및 홍보 전략으로 활용하고 있는 USP 사례를 통해 기업의 효과적이고 지속적인 브랜드 경쟁우위를 유지하기 위한 방법을 알아보았다.

• Journal of Life Science
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• v.20 no.7
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• pp.1005-1011
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• 2010

$\gamma$-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. GABA transporters (GATs) control extracellular GABA levels by reuptake of released GABA from the synaptic cleft. However, how GATs are regulated has not yet been elucidated. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of GAT1, the major isoform in the brain and find a specific interaction with the ubiquitin-specific protease 14 (Usp14), a deubiquitinating enzyme. Usp14 protein bound to the tail region of GAT1 and GAT2 but not to other GAT members in the yeast two-hybrid assay. The C-terminal region of Usp14 is essential for interaction with GAT1. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. An antibody to GAT1 specifically co-immunoprecipitated Usp14 from mouse brain extracts. These results suggest that Usp14 may regulate the number of GAT1 at the cell surface.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1957-1962
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• 2012

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

• Anxiety and mood
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• v.15 no.2
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• pp.122-126
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• 2019

Objective : Dynamic proteolysis, through the ubiquitin-proteasome system, is an important molecular mechanism for the constant regulation of synaptic plasticity and stress responses in humans. In this study, we examined whether genetic variants in the ubiquitin-specific peptidase (USP) genes were associated with psychological traits of resilience and susceptibility to neuropsychiatric disorders for each gender. Methods : A total of 344 Korean healthy youths (190 males, 154 females) were included in the study. A genotyping of rs2241646 of USP2 and rs346006 of USP46 was performed. The Connor-Davidson Resilience Scale and Brief Fear of Negative Evaluation Scale were administered for measuring trait resilience and social anxiety, respectively. The genetic associations of the USP variants were tested using multiple analyses of covariance with psychological traits as dependent variables after controlling for age in each gender. Results : For USP2 rs2241646, women with the TT genotype showed significantly higher resilience and lower social anxiety, as compared to those carrying the C allele. There were no associations between USP46 rs346005 and the psychological traits in both genders. Conclusions : The present study showed a possible genetic association between the USP2 rs2241646 and stress resilience and trait anxiety in women. The findings suggest that ubiquitin-proteasome system may be related to the resilience and susceptibility to stress-related neuropsychiatric disorders such as anxiety disorders, possibly through the regulation of dynamic proteolysis responses to stress.