• BMB Reports
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• 제56권8호
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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.

• 생명과학회지
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• 제20권7호
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• pp.1005-1011
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• 2010

$\gamma$-aminobutyric acid (GABA)는 중추신경계에서 억제성으로 작용하는 주요한 신경전달물질이다. GABA 수송체(GAT)는 연접간격에 존재하는 GABA를 세포 내로 재 흡수하여 GABA의 농도를 조절한다. 그런데 GABA 수송체가 어떻게 조절되는지는 아직 밝혀지지 않았다. 본 연구에서는 효모 two-hybrid system을 사용하여 뇌의 주요 GABA 수송체인 GAT1의 C-말단과 특이적으로 결합하는 ubiquitin-specific protease 14 (Usp14)를 분리하였다. Usp14는 GABA 수송체 GAT1및 GAT2와는 결합하지만, 다른 GAT isoform과는 결합하지 않았다. GAT1과의 결합에는 Usp14의 C-말단부위가 필수적으로 관여함을 확인하였다. 또한 이 단백질간의 결합을 GST pull-down assay로 확인하였으며, 생쥐 뇌 균질액의 co-immunoprecipitation을 통하여 in vivo에서도 GAT1과 Usp14가 결합함을 확인하였다. 이러한 결과들은 Usp14가 GAT1과 결합하여 세포막에 존재하는 GAT1의 수를 조절하는 역할을 할 가능성을 시사한다.

• 한국동물학회지
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• 제37권3호
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• pp.324-330
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• 1994

The multicatalvtic 205 proteasome consisting of 12-15 subunits of 22-35 kDa is the catalytic core of the ATP/ubiquitin-dependent 26S protease complex that also is comprised of multiple subunits of 22-110 KDa. In order to determine whether the proteolvtic activities change during muscle development, the enzyme preparations were obtained from 11-, 14- and 17-day old chick embryonic muscle using a BioGel A-1.5m column. The 26S complex preparation from 14- or 17-day old muscle hvdr olvz e d both N -s uccinvl- Le u- Le u -Val-Tvr-7- amido -4- methvlco umarin ( Suc- LLVY- AMC) and ubiquitin-Ivsozvme conjugates about 50% as well as that from 11-day old muscle. In addition, the activity of 20S proteBsome against Suc-LLVY-AMC also decreased by about 20-30%. However, the protein level of 265 complex remained constant during the entire development period, while that of 205 proteasome increased 5- to 6-fold, as analyzed by nondenaturins polyacrvlamide gel elenrophoresis followed by immunoblot analysis using the antibodies raised against the purified enzymes. Thus, the specific activity of 20S proteasome against the peptide must decrease rather dramatically during the muscle development. These results suggest that the development-dependent changes in the proteolytic activities of both 20S proteasome and 26S protease complect from embryonic muscle are due to alterations in the expression of certain subunits in the enzvmes that are responsible for their specific cataIVtic functions but not to overall changes in the enzyme amounts.