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CD9-association with PIP2 areas is regulated by a CD9 salt bridge. CD9与PIP2区域的结合受CD9盐桥调控。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-18 DOI: 10.1002/2211-5463.70084
Yahya Homsi, Sara C Konopka, Thorsten Lang
{"title":"CD9-association with PIP<sub>2</sub> areas is regulated by a CD9 salt bridge.","authors":"Yahya Homsi, Sara C Konopka, Thorsten Lang","doi":"10.1002/2211-5463.70084","DOIUrl":"https://doi.org/10.1002/2211-5463.70084","url":null,"abstract":"<p><p>Tetraspanins are membrane proteins involved in multiple cellular functions, which they regulate by means of tetraspanin-enriched microdomains. While many tetraspanin-associated processes are regulated by intracellular signaling, possibly through the crosstalk between intracellular tetraspanin segments and second messengers like PIP<sub>2</sub>, this molecular crosstalk has remained largely unknown. To improve our understanding of this crosstalk, we investigate the possible relationship between an intracellular salt bridge of the tetraspanin CD9 and PIP<sub>2</sub>. We find that CD9 readily associates with PIP<sub>2</sub>-rich areas, in contrast to its interaction partner EWI-2. The opening of the CD9 salt bridge lowers the abundance of CD9 in these PIP<sub>2</sub> areas. Instead, open-CD9 can be located in regions that are more strongly populated with EWI-2, promoting CD9-EWI-2 association. This study uncovers the process of an intracellular salt bridge regulating the association of CD9 with PIP<sub>2</sub>-enriched areas. This points toward a possible link between intracellular tetraspanin segments and signaling.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polydatin ameliorates ovalbumin-induced asthma in a rat model through NCOA4-mediated ferroautophagy and ferroptosis pathway. 多柚素通过ncoa4介导的铁自噬和铁凋亡途径改善卵清蛋白诱导的大鼠哮喘模型。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-16 DOI: 10.1002/2211-5463.70090
Wei Li, Yuwei Tang, Wenkang Liu, Fang Fang, Jiepeng Wang, Chaoyi Fang
{"title":"Polydatin ameliorates ovalbumin-induced asthma in a rat model through NCOA4-mediated ferroautophagy and ferroptosis pathway.","authors":"Wei Li, Yuwei Tang, Wenkang Liu, Fang Fang, Jiepeng Wang, Chaoyi Fang","doi":"10.1002/2211-5463.70090","DOIUrl":"https://doi.org/10.1002/2211-5463.70090","url":null,"abstract":"<p><p>Asthma is one of the most prevalent chronic diseases worldwide. In this study, we aimed to explore whether polydatin can achieve therapeutic effects in experimental asthma in a rat model by suppressing ferroptosis and its potential mechanism of inhibiting ferroptosis. We established a rat asthma model, and five experimental groups were established: the control group, model group, polydatin group, 3-MA group, and Fer-1 group. We compared general conditions, behavioral changes, Fe<sup>3+</sup>deposition, pathological changes, pulmonary function, serum IgE levels, ferroautophagy-related genes, and ferroptosis-related genes expression among the groups. Following the polydatin intervention, the mental state of the rats stabilized, their fur condition improved, and both food intake and body weight increased. The incubation period of asthma lengthened, and they sneezed and scratched less frequently. Additionally, polydatin reduced serum IgE levels and Fe<sup>3+</sup> deposition, enhanced lung function and pathological alterations, and also downregulated the expression of nuclear receptor coactivator 4 (NCOA4), Bcl-2 homologous domain protein (Beclin1), Fe<sup>2+</sup>, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung tissue. Levels of ferritin heavy chain 1 (FTH1), ubiquitin-binding protein p62 (P62), glutathione (GSH), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were all upregulated. In conclusion, in this rat model, polydatin was capable of reducing Fe<sup>2+</sup> overload by inhibiting the NCOA4-mediated ferroautophagy. This, in turn, inhibited ferroptosis in the lung tissues, thereby alleviating asthma symptoms. Further studies, including clinical trials, are required to validate this result.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional parameters of spermatozoa obtained by a new selection device. 用一种新的选择装置获得的精子功能参数。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-14 DOI: 10.1002/2211-5463.70073
Julio C Chávez, Paulina Torres, Gabriela Carrasquel-Martínez, María G Figueroa-Méndez, Diana Flores, Lina Villar, Israel Maldonado, Marcela B Trevino, Claudia Treviño
{"title":"Functional parameters of spermatozoa obtained by a new selection device.","authors":"Julio C Chávez, Paulina Torres, Gabriela Carrasquel-Martínez, María G Figueroa-Méndez, Diana Flores, Lina Villar, Israel Maldonado, Marcela B Trevino, Claudia Treviño","doi":"10.1002/2211-5463.70073","DOIUrl":"https://doi.org/10.1002/2211-5463.70073","url":null,"abstract":"<p><p>The success of assisted reproduction techniques (ARTs) is based on the selection of gametes with optimal characteristics. This is critical for male gametes, since among the large number of cells present in semen, many may have unnoticeable DNA damage and compromised membrane integrity, among other alterations. In this work, we examined the use of the LensHooke CA0™ device (CA0 chamber) as a promising sperm separation method for ARTs, analyzing both normozoospermic and teratozoospermic samples. Additionally, we compared fertilization rates with IVF and ICSI procedures using Teratozoospermic samples. As reference for comparison, we used the current standard for sperm selection, density gradient centrifugation. Using CA0 chambers and DGC, we obtained comparable sperm recovery numbers, membrane potential (in Normozoospermic samples) and motility parameters. The progesterone-induced intracellular Ca<sup>2+</sup> increase was only slightly greater in sperm selected with DGC compared to CA0 chambers. Finally, no differences were observed in IVF and ICSI fertilization rates between Tz sperm separated with DGC and CA0 chambers. Overall, we conclude that the quantity and quality of sperm selected with CA0 chambers is comparable to that obtained with DGC, without compromising reproducibility. Importantly, CA0 chambers offer key practical and methodological advantages, resulting in a faster, simpler and more affordable sperm selection method.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity. 表征WAC与R2TP和TTT伴侣复合物的相互作用,将葡萄糖和谷氨酰胺的可用性与mTORC1活性联系起来。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-13 DOI: 10.1002/2211-5463.70085
Sofía Cabezudo, Natalia Cuervo, Carmen García-Martín, Andrés López-Perrote, Clara Reglero, Adrián Maqueda-Real, Ana González-Corpas, Marina Serna, Diego Megías, Alejo Efeyan, Solip Park, Oscar Llorca
{"title":"Characterization of WAC interactions with R2TP and TTT chaperone complexes linking glucose and glutamine availability to mTORC1 activity.","authors":"Sofía Cabezudo, Natalia Cuervo, Carmen García-Martín, Andrés López-Perrote, Clara Reglero, Adrián Maqueda-Real, Ana González-Corpas, Marina Serna, Diego Megías, Alejo Efeyan, Solip Park, Oscar Llorca","doi":"10.1002/2211-5463.70085","DOIUrl":"https://doi.org/10.1002/2211-5463.70085","url":null,"abstract":"<p><p>TELO2-TTI1-TTI2 (TTT) and R2TP are multi-subunit chaperones that cooperate with HSP90 to assemble matured complexes of the PIKK family of kinases, including mTOR complex 1 (mTORC1). WAC, a protein previously implicated in transcription, H2B ubiquitination, and autophagy, was recently identified as a regulator of mTORC1 in response to glucose and glutamine availability, acting in concert with R2TP and TTT. However, the molecular basis of the interactions of WAC with R2TP and TTT and their role in mTORC1 regulation remains poorly defined. Here, we characterized the interactions of WAC with mTOR, R2TP, and TTT and how these are affected by nutrient conditions. Using purified proteins, we establish that WAC directly binds to mTOR-mLST8, R2TP, and TELO2, but not TTI1 and TTI2. In cells, WAC is part of complexes containing components of mTORC1, R2TP, and TTT, and these associations are modulated by nutrient availability. Notably, WAC and TELO2 strongly associate with mTOR under glucose and glutamine deprivation, and these interactions are weakened minutes after nutrient refeeding. These dynamics correlate with changes in mTORC1 activity. Transcriptomic and proteomic analysis shows that WAC, mTOR, R2TP, and TTT are co-expressed across several human cancers, supporting that WAC is part of a functional pathway with mTOR, R2TP, and TTT. Together, our findings reveal the formation and disassembly of a WAC complex with mTOR and TELO2 that contributes to regulate mTORC1 in response to glucose and glutamine availability.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two-way inhibition of PAX5 transcriptional activity by PAX5::CBFA2T3. PAX5::CBFA2T3对PAX5转录活性的双向抑制
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-11 DOI: 10.1002/2211-5463.70087
Reina Ueno, Aki Terasaki, Yuiko Imai, Yuri Kimura, Yuna Kojima, Misa Irie, Koya Odaira, Mina Noura, Shuichi Okamoto, Takahiko Yasuda, Shinobu Tsuzuki, Hitoshi Kiyoi, Fumihiko Hayakawa
{"title":"Two-way inhibition of PAX5 transcriptional activity by PAX5::CBFA2T3.","authors":"Reina Ueno, Aki Terasaki, Yuiko Imai, Yuri Kimura, Yuna Kojima, Misa Irie, Koya Odaira, Mina Noura, Shuichi Okamoto, Takahiko Yasuda, Shinobu Tsuzuki, Hitoshi Kiyoi, Fumihiko Hayakawa","doi":"10.1002/2211-5463.70087","DOIUrl":"https://doi.org/10.1002/2211-5463.70087","url":null,"abstract":"<p><p>PAX5 promotes B-cell differentiation by transcriptional activation of B-lineage-specific genes. Chromosomal rearrangements in PAX5 account for 2-3% of B-ALL cases, and most lead to the expression of in-frame fusion transcripts. These fusions can encode chimeric proteins composed of the N-terminal portion of PAX5 and the C-terminal region of a variety of heterogeneous fusion partners. We analyzed the function of PAX5::CBFA2T3 (PAX5-C), a fusion protein found in B-cell acute lymphoblastic leukemia. PAX5-C strongly repressed PAX5 transcriptional activity in luciferase assays. In co-immunoprecipitation assays, PAX5-C bound to PAX5 and HDAC1/3. However, neither HDAC knockdown nor treatment with a HDAC inhibitor showed any effect on the repression of PAX5 transactivity by PAX5-C. In addition, PAX5-C with DNA binding-defective mutations (PAX5 M-C) could still repress PAX5 transactivity; however, the repression of PAX5 transactivity by PAX5 M-C was abolished by inhibition or knockdown of HDAC. These findings indicate that PAX5-C exhibits two mechanisms of repression: a DNA binding-dependent and a HDAC-dependent mechanism, with either being sufficient for the repression of PAX5 transactivity by PAX5-C. We performed ChIP-qPCR under conditions of the luciferase assay and inferred that these two mechanisms involved the inhibition of direct binding of PAX5 to the promoter due to promoter occupancy by PAX5-C, and recruitment of HDAC1/3 to the PAX5 transcription complex by the binding of PAX5-C to PAX5 on the promoter. The present results provide novel insight into the mechanisms of how PAX5-fusion proteins inhibit PAX5 function.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families. 由IqgC控制的肌动蛋白动力学,在IQGAP和真菌GAP1家族之间的十字路口的一个RasGAP。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-11 DOI: 10.1002/2211-5463.70083
Vedrana Filić, Darija Putar, Lucija Mijanović, Igor Weber
{"title":"Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families.","authors":"Vedrana Filić, Darija Putar, Lucija Mijanović, Igor Weber","doi":"10.1002/2211-5463.70083","DOIUrl":"https://doi.org/10.1002/2211-5463.70083","url":null,"abstract":"<p><p>In addition to transmitting receptor-mediated signals to adjust the gene expression profile of the cell, small GTPases of the Ras family also control the remodelling of the actin cytoskeleton. The conversion of Ras GTPases from their active to their inactive form is controlled by Ras GTPase-activating proteins (RasGAPs). IqgC, a RasGAP from Dictyostelium discoideum, was originally assigned to the IQGAP family, but its sequence and recent functional analyses show that IqgC is more closely related to RasGAPs from the GAP1 family of fungi. IqgC has two prominent domains, a RasGAP domain and a C-terminal RGCt domain, and interacts with Ras, Rab and Rap GTPases, but shows GTPase-promoting activity only towards Ras. IqgC suppresses macroendocytosis but supports cell-substratum adhesion and directed cell migration. Its localisation to macroendocytic cups is mediated by the RasGAP domain, whereas its localisation in ventral focal adhesions is mediated by the RGCt domain. We hypothesise that IqgC plays an important role in the balance between the competing feeding and migratory behaviour of amoeboid D. discoideum cells.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microfluidic electro-viscoelastic manipulation of extracellular vesicles. 细胞外囊泡的微流体电粘弹性操纵。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-09 DOI: 10.1002/2211-5463.70080
Seyedamirhosein Abdorahimzadeh, Éva Bozó, Zikrullah Bölükkaya, Artem Zhyvolozhnyi, Anatoliy Samoylenko, Henrikki Liimatainen, Seppo J Vainio, Caglar Elbuken
{"title":"Microfluidic electro-viscoelastic manipulation of extracellular vesicles.","authors":"Seyedamirhosein Abdorahimzadeh, Éva Bozó, Zikrullah Bölükkaya, Artem Zhyvolozhnyi, Anatoliy Samoylenko, Henrikki Liimatainen, Seppo J Vainio, Caglar Elbuken","doi":"10.1002/2211-5463.70080","DOIUrl":"https://doi.org/10.1002/2211-5463.70080","url":null,"abstract":"<p><p>Microfluidic technology has created new opportunities for developing innovative tools for biological applications. Given the significance of extracellular vesicles (EVs), extensive research has focused on developing microfluidic techniques for EV isolation. This research protocol presents electro-viscoelastic microfluidics as a novel approach for manipulating EVs. The system leverages the viscoelasticity of the suspending medium along with an externally applied electric field to alter EV motion within a microchannel. These findings suggest that our electro-viscoelastic microfluidic system has the potential for further development to be used for EV isolation.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NMR screening of low molecular weight inhibitors targeting the papain-like protease (PLPro) of SARS-CoV-2. 针对SARS-CoV-2的木瓜蛋白酶(PLPro)低分子量抑制剂的NMR筛选。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-01 DOI: 10.1002/2211-5463.70082
Dennis J Pyper, Sridhar Sreeramulu, Benjamin T Lanham, Elizabeth M Engle, David Fushman, Harald Schwalbe
{"title":"NMR screening of low molecular weight inhibitors targeting the papain-like protease (PLPro) of SARS-CoV-2.","authors":"Dennis J Pyper, Sridhar Sreeramulu, Benjamin T Lanham, Elizabeth M Engle, David Fushman, Harald Schwalbe","doi":"10.1002/2211-5463.70082","DOIUrl":"https://doi.org/10.1002/2211-5463.70082","url":null,"abstract":"<p><p>The Papain-like protease (PLPro) from SARS-CoV-2 plays an important role in the cleavage of the polyproteins Pp1a and Pp1ab as well as in the suppression of the immune response by deISG15ylation. Considerable effort is therefore devoted to developing low molecular weight inhibitors as starting points for antiviral drugs. Here, we present the results of an NMR screening study of PLPro for binding to the DSI-poised fragment library containing 607 compounds. Based on saturation-transfer difference (STD)- and WaterLOGSY-NMR experiments, we identified 86 binding compounds. We prioritized five candidates for further in-depth analysis. For three of those, we determined dissociation constants and two distinct binding sites on PLPro. These compounds could serve as a basis for future drug design studies in medicinal chemistry.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liver-specific lncRNAs associated with liver cancers. 与肝癌相关的肝脏特异性lncrna
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-01 DOI: 10.1002/2211-5463.70079
Olga Y Burenina, Roman K Makarchenko, Maria P Rubtsova, Olga A Dontsova
{"title":"Liver-specific lncRNAs associated with liver cancers.","authors":"Olga Y Burenina, Roman K Makarchenko, Maria P Rubtsova, Olga A Dontsova","doi":"10.1002/2211-5463.70079","DOIUrl":"https://doi.org/10.1002/2211-5463.70079","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are transcripts with a length more than 200 nt, which do not encode proteins and act just as RNA molecules. In general, lncRNAs have much more distinct tissue specificity than proteins, as they usually realize more peculiar regulatory functions. Their expression levels are often altered in a response to stress conditions, metabolic changes, development of different diseases, and carcinogenesis. Cancer-associated lncRNAs are widely considered as perspective and useful biomarkers. Thus, development of clinical tests, which include tissue-specific and cancer-specific lncRNAs, might significantly contribute to cancer diagnostics and/or prognosis of the disease. A number of lncRNAs is known to be dysregulated in liver tumors and considered as probable biomarkers. However, most of them are rather universally well-known lncRNAs associated with various cancers. In the present review, we aimed to shed light on other lncRNAs with preferential expression in liver and/or liver tumors, for example, LINC01554, LINC01093, LINC01348, LINC02428, FAM99B, etc. We summarized recent discoveries unveiling their dysregulation in liver malignancies and related cellular mechanisms in which they are involved and considered their significance as probable liver cancer biomarkers.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The E3 ubiquitin ligase, RNF219, suppresses CNOT6L expression to exhibit antiproliferative activity. E3泛素连接酶RNF219抑制CNOT6L的表达以显示抗增殖活性。
IF 2.8 4区 生物学
FEBS Open Bio Pub Date : 2025-07-01 DOI: 10.1002/2211-5463.70081
Shou Soeda, Melissa Montrose, Akinori Takahashi, Risa Ishida, Sandrine Burriel, Nao Ohmine, Tohru Natsume, Shungo Adachi, Minsoo Kim, Tadashi Yamamoto
{"title":"The E3 ubiquitin ligase, RNF219, suppresses CNOT6L expression to exhibit antiproliferative activity.","authors":"Shou Soeda, Melissa Montrose, Akinori Takahashi, Risa Ishida, Sandrine Burriel, Nao Ohmine, Tohru Natsume, Shungo Adachi, Minsoo Kim, Tadashi Yamamoto","doi":"10.1002/2211-5463.70081","DOIUrl":"https://doi.org/10.1002/2211-5463.70081","url":null,"abstract":"<p><p>Despite the increasing evidence of the role of CCR4-NOT complex in posttranscriptional gene regulation, relatively little is known about its mode of action. In a search for novel CCR4-NOT interacting partners, we carried out mass spectrometry analysis of immunoprecipitates with antibodies against four different CCR4-NOT subunits and identified RNF219, ring finger protein 219. A pull-down assay revealed that the C-terminal part of RNF219 directly binds to the CNOT1 DUF3819 domain and is associated with ubiquitin ligase activity. RNF219 knock-down in HEK293T cells resulted in elevated expression of CNOT6L, accompanied by increased cell proliferation. The apparent antiproliferative activity of RNF219 was inversely correlated with the level of CNOT6L. Furthermore, RNF219 ubiquitinated CNOT6L in vitro. Our data suggest that RNF219 suppress CNOT6L expression through proteasome-mediated protein degradation. Intriguingly, low expression of RNF219 was associated with poor prognosis of triple-negative breast cancer patients. However, further studies would be required to confirm whether the impact of RNF219 activity on cancer progression is mediated by the CCR4-NOT complex.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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