• Molecules and Cells
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• 제27권3호
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• pp.359-363
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• 2009

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tumor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.

• Molecules and Cells
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• 제41권3호
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• pp.168-178
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• 2018

Intracellular communication via ubiquitin (Ub) signaling impacts all aspects of cell biology and regulates pathways critical to human development and viability; therefore aberrations or defects in Ub signaling can contribute to the pathogenesis of human diseases. Ubiquitination consists of the addition of Ub to a substrate protein via coordinated action of E1-activating, E2-conjugating and E3-ligating enzymes. Approximately 40 E2s have been identified in humans, and most are thought to be involved in Ub transfer; although little information is available regarding the majority of them, emerging evidence has highlighted their importance to human health and disease. In this review, we focus on recent insights into the pathogenetic roles of E2s (particularly the ubiquitin-conjugating enzyme E2O [UBE2O]) in debilitating diseases and cancer, and discuss the tantalizing prospect that E2s may someday serve as potential therapeutic targets for human diseases.

• Molecules and Cells
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• 제39권3호
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• pp.250-257
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• 2016

Abiotic stresses such as drought and low temperature critically restrict plant growth, reproduction, and productivity. Higher plants have developed various defense strategies against these unfavorable conditions. CaPUB1 (Capsicum annuum Putative U-box protein 1) is a hot pepper U-box E3 Ub ligase. Transgenic Arabidopsis plants that constitutively expressed CaPUB1 exhibited drought-sensitive phenotypes, suggesting that it functions as a negative regulator of the drought stress response. In this study, CaPUB1 was over-expressed in rice (Oryza sativa L.), and the phenotypic properties of transgenic rice plants were examined in terms of their drought and cold stress tolerance. Ubi:CaPUB1 T3 transgenic rice plants displayed phenotypes hypersensitive to dehydration, suggesting that its role in the negative regulation of drought stress response is conserved in dicot Arabidopsis and monocot rice plants. In contrast, Ubi:CaPUB1 progeny exhibited phenotypes markedly tolerant to prolonged low temperature ($4^{\circ}C$) treatment, compared to those of wild-type plants, as determined by survival rates, electrolyte leakage, and total chlorophyll content. Cold stress-induced marker genes, including DREB1A, DREB1B, DREB1C, and Cytochrome P450, were more up-regulated by cold treatment in Ubi:CaPUB1 plants than in wild-type plants. These results suggest that CaPUB1 serves as both a negative regulator of the drought stress response and a positive regulator of the cold stress response in transgenic rice plants. This raises the possibility that CaPUB1 participates in the cross-talk between drought and low-temperature signaling pathways.

• 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.