• Experimental and Molecular Medicine
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• 제50권12호
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• pp.8.1-8.12
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• 2018

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

• BMB Reports
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• 제54권12호
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• pp.592-600
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• 2021

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly population and is caused by the loss of dopaminergic neurons. PD has been predominantly attributed to mitochondrial dysfunction. The structural alteration of α-synuclein triggers toxic oligomer formation in the neurons, which greatly contributes to PD. In this article, we discuss the role of several familial PD-related proteins, such as α-synuclein, DJ-1, LRRK2, PINK1, and parkin in mitophagy, which entails a selective degradation of mitochondria via autophagy. Defective changes in mitochondrial dynamics and their biochemical and functional interaction induce the formation of toxic α-synuclein-containing protein aggregates in PD. In addition, these gene products play an essential role in ubiquitin proteasome system (UPS)-mediated proteolysis as well as mitophagy. Interestingly, a few deubiquitinating enzymes (DUBs) additionally modulate these two pathways negatively or positively. Based on these findings, we summarize the close relationship between several DUBs and the precise modulation of mitophagy. For example, the USP8, USP10, and USP15, among many DUBs are reported to specifically regulate the K48- or K63-linked de-ubiquitination reactions of several target proteins associated with the mitophagic process, in turn upregulating the mitophagy and protecting neuronal cells from α-synuclein-derived toxicity. In contrast, USP30 inhibits mitophagy by opposing parkin-mediated ubiquitination of target proteins. Furthermore, the association between these changes and PD pathogenesis will be discussed. Taken together, although the functional roles of several PD-related genes have yet to be fully understood, they are substantially associated with mitochondrial quality control as well as UPS. Therefore, a better understanding of their relationship provides valuable therapeutic clues for appropriate management strategies.

• Journal of Ginseng Research
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• 제48권1호
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• pp.40-51
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• 2024

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-kB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (β-TrCP1), a substrate recognition subunit for SCF^β-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

• 한국체육학회지인문사회과학편
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• 제55권4호
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• pp.507-516
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• 2016

본 연구는 지구성 운동 후 안정시 PGC-1α mRNA와 단백질의 안정성이 PPARβ/δ의 영향을 받는지 확인하는 것이다. 전기 자극 유전자 전이법(electroporation; EPO)을 이용하여 PPARβ/δ와 empty vector(EV) 유전자를 각각 생쥐의 왼쪽과 오른쪽 tibialis anterior(TA)근육에 전이하였으며, 처치하지 않은 대조군(control)과 1회 지구성 운동 후 시간에 경과에 따른 mRNA와 단백질을 비교하였다. 생쥐는 5시간 수영 운동을 1회 실시하였으며, 운동 직후(0h), 24시간(24h) 및 54시간(h)이 경과한 후 TA근육을 적출하였다. 운동 직후(0h) 대조군, EV 및 PPARβ/δ가 과발현된 근육의 PGC-1α mRNA는 좌업 그룹보다 각각 6.8배(p<.001)배, 6.2배(p<.001) 및 7.1배(p<.001) 증가하였으나, 24h 및 54h에 좌업 그룹수준으로 회복되었다. 운동 후 24h에 EV가 처치된 근육은 PGC-1α 및 PGC-1α ubiquitination이 좌업 그룹보다 각각 2.2배 및 1.74배 증가하였으나, 운동 후 54h에 좌업 그룹수준으로 회복되었다. PPARβ/δ 처치 그룹의 PGC-1α는 운동 후 24h와 54h에 좌업 그룹보다 각각 2.5배와 2.2배 증가하였으나 PGC-1α ubiquitination은 증가하지 않았다. 따라서 PPARβ/δ 과발현은 지구성 운동에 의한 PGC-1α mRNA 단백질 안정성에 영향을 미치지 않는다. 그러나 PPARβ/δ 과발현은 지구성 운동으로 증가된 PGC-1α mRNA가 단백질로 전환된 후 PGC-1α의 안정성을 증가시킨다.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2018년도 춘계학술대회
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• pp.169-169
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• 2018

• Molecules and Cells
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• 제39권11호
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• pp.834-840
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• 2016

Caenorhabditis elegans (C. elegans) utilizes two different cell-cycle modes, binucleations during the L1 larval stage and endoreduplications at four larval moltings, for its postembryonic intestinal development. Previous genetic studies indicated that CDC-25.2 is specifically required for binucleations at the L1 larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the C. elegans ${\beta}$-TrCP ortholog, appears to function as a repressor of CDC-25.2 to prevent excess intestinal divisions. We previously reported that intestinal hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi depletion of cdc-25.2. Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN-23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2 to repress their activities for proper transition of cell-cycle modes during the C. elegans postembryonic intestinal development. In addition, for the first time that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates ubiquitination for timely regulation of their activities during the intestinal development.

• BMB Reports
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• 제51권6호
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• pp.265-273
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• 2018

Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed "tauopathies" which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensively studied as a major pharmacological target for AD therapy. However, in addition to phosphorylation events, tau undergoes a number of diverse posttranslational modifications (PTMs) which appear to be controlled by complex crosstalk. It remains to be elucidated which of the PTMs or their combinations have pro-aggregation or anti-aggregation properties. In this review, we outline the consequences of and communications between several key PTMs of tau, such as acetylation, phosphorylation, and ubiquitination, focusing on their roles in aggregation and degradation. We place emphasis on the structure of tau protofilaments from the human AD brain, which may be good targets to modulate etiological PTMs which cause tau aggregation.

• 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.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.150-150
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• 2017

Plants suffer from various abiotic stresses among them; soil salinity is one of major adverse factor in declining agricultural productivity. So, development of salt stress tolerance crops have potential role to increase crop production. The RING finger proteins are known to play crucial roles in abiotic stress environment to plants. In this study, we identified one Salt-responsive Really${\underline{I}nteresting}$ ${\underline{n}ew}$ ${\underline{g}ene}$ (RING) E3 ubiquitin ligase gene OsSIRF1 from rice root tissues during salt stress and studied its molecular function. Expression of OsSIRF1 was induced under various abiotic stress conditions, including salt, heat, drought, and ABA. Result of an in vitro ubiquitination assay clearly showed that OsSIRF1 Possess an E3 ligase activity. Moreover, OsSIRF1 was found to be localized to the nucleus within the cell. Heterogeneous overexpression of OsSIRF1 in Arabidopsis improved seed germination and increased root length under salt and Manitol stress conditions. Taking together, these results suggested that OsSIRF1 may be associated with plant responses to abiotic stressors and positively regulates salt and osmotic stress environment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2313-2318
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• 2014

Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.