• BMB Reports
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• 제41권6호
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• pp.435-443
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• 2008

Post-translational modifiers can alter the function of proteins in many different ways. The conjugation of ubiquitin (Ub) and ubiqutin-like modifiers (Ubls) to proteins has been shown to be especially crucial in regulating a variety of cellular processes including the cell cycle, growth control, quality control, localization and many more. It is a highly dynamic process and involves a number of enzymes called E1, E2 and E3. Ub and Ubls are removed from the target proteins by deubiquitinating enzymes (DUBs) or Ubl-specific proteases (ULPs), thereby deconjugation can act as an additional level of control over the ubiquitin-conjugation system. In addition, DUBs and ULPs are responsible for activating Ub and Ubls from their inactive corresponding precursor forms. Here we review recent progress in molecular details of these deconjugating enzymes of Ubls.

• Molecules and Cells
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• 제28권5호
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• pp.463-472
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• 2009

Although the possible cellular roles of several ubiquitin-specific proteases (UBPs) were identified in Arabidopsis, almost nothing is known about UBP homologs in rice, a monocot model plant. In this report, we searched the rice genome database (http://signal.salk.edu/cgi-bin/RiceGE) and identified 21 putative UBP family members (OsUBPs) in the rice genome. These OsUBP genes each contain a ubiquitin carboxyl-terminal hydrolase (UCH) domain with highly conserved Cys and His boxes and were subdivided into 9 groups based on their sequence identities and domain structures. RT-PCR analysis indicated that rice OsUBP genes are expressed at varying degrees in different rice tissues. We isolated a full-length cDNA clone for OsUBP6, which possesses not only a UCH domain, but also an N-terminal ubiquitin motif. Bacterially expressed OsUBP6 was capable of dismantling K48-linked tetra-ubiquitin chains in vitro. Quantitative real-time RT-PCR indicated that OsUBP6 is constitutively expressed in different tissues of rice plants. An in vivo targeting experiment showed that OsUBP6 is predominantly localized to the nucleus in onion epidermal cells. We also examined how knock-out of OsUBP6 affects developmental growth of rice plants. Although homozygous T3 osubp6 T-DNA insertion mutant seedlings displayed slower growth relative to wild type seedlings, mature mutant plants appeared to be normal. These results raise the possibility that loss of OsUBP6 is functionally compensated for by an as-yet unknown OsUBP homolog during later stages of development in rice plants.

• 생명과학회지
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• 제30권5호
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• pp.483-490
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• 2020

유비퀴틴 시스템은 ubiquitin ligases와 deubiquitinases (DUBs)에 의해 타겟 기질의 ubiquitination 유무에 따라 안정화, 활성화, 국소화 및 상호작용을 변화시키고 암 발병의 관여하는 다양한 생물학적 과정을 조절한다. DUBs는 촉매 domain에 따라 6그룹으로 나뉘어지는데, 그 중에서 OTU 그룹 내 대부분의 DUB는 세포의 연속적 신호반응(cell signaling cascade)을 조절할 수 있다. 특이하게도 OTU 그룹에 속하는 otubain 1 (OTUB1)은 정규적(canonical) 활성과 비정규적(non-canonical) 활성을 모두 가지고 있다. 본 보고에서는 OTUB1의 canonical, non-canonical 활성 조절에 있어서 다양한 신호전달경로 및 OTUB1의 역할에 대해 기술하였다. OTUB1은 이 두 종류의 활성 경로를 통하여, OTUB1은 암 관련 신호 전달 체계에 중요한 FOXM1, ERα, KRAS 및 EMT를 조절하고 암세포 증식 및 전이 능력 향상 및 항암제에 대한 내성을 나타낸다. 또한 임상적으로 전이성 및 종양 분화도가 높은 암 조직에서 OTUB1의 발현이 높으며, 이에 따라 환자의 생존율이 감소하는 등 나쁜 예후를 나타낸다. 따라서, 임상적으로 적용할 수 있는 OTUB1 억제제의 개발이 이루어진다면 OTUB1은 종양 치료에 있어 중요한 진단마커이자 치료적인 타겟이 될 수 있다.

• BMB Reports
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• 제52권3호
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• pp.181-189
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• 2019

Cancer remains a life-threatening disease and accounts for the major mortality rates worldwide. The practice of using biomarkers for early detection, staging, and customized therapy may increase cancer patients' survival. Deubiquitinating enzymes (DUBs) are a family of proteases that remove ubiquitin tags from proteins of interest undergoing proteasomal degradation. DUBs play several functional roles other than deubiquitination. One of the important roles of DUBs is regulation of tumor progression. Several reports have suggested that the DUB family members were highly-elevated in various cancer cells and tissues in different stages of cancer. These findings suggest that the DUBs could be used as drug targets in cancer therapeutics. In this review, we recapitulate the role of the DUB family members, including ubiquitin-specific protease, otubain protease, and important candidates from other family members. Our aim was to better understand the connection between DUB expression profiles and cancers to allow researchers to design inhibitors or gene therapies to improve diagnosis and prognosis of cancers.

• BMB Reports
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• 제52권2호
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• pp.113-118
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• 2019

The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.