FEBS Open Bio最新文献_第9页

Biochemical characterization of the human ubiquitous glucose-6-phosphatase in neutrophil granulocytes 中性粒细胞中人类无处不在的葡萄糖-6-磷酸酶的生化特征。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-15 DOI: 10.1002/2211-5463.13924

Zsigmond Lédeczi, Klaudia Németh, Tamás Kardon

{"title":"Biochemical characterization of the human ubiquitous glucose-6-phosphatase in neutrophil granulocytes","authors":"Zsigmond Lédeczi, Klaudia Németh, Tamás Kardon","doi":"10.1002/2211-5463.13924","DOIUrl":"10.1002/2211-5463.13924","url":null,"abstract":"Glucose-6-phosphatase-β (G6PC3) is a ubiquitous phosphatase present in the endoplasmic reticulum, which, unlike G6PC1, is not responsible for maintaining blood glucose level under starvation. Recently, G6PC3 has been shown to play an important role in neutrophil granulocytes, eliminating the toxic metabolite 1,5-anhydroglucitol-6-phosphate. The present study aimed to look for alternative substrates for the enzyme and outline the expression changes in the parts of this multicomponent system during neutrophil granulocyte differentiation. We determined the kinetic characteristics of recombinant human G6PC3 towards different sugar phosphates, and the transport of these compounds was also measured in rat liver microsomes. We found that all investigated sugar phosphates are substrates for G6PC3, although their microsomal transport is much slower than that of glucose-6-phosphate. Using the HL-60 promyelocytic leukemia cell line as an in vitro model system for myeloid differentiation, we found no significant differences in enzyme expression and phosphatase activity latency between undifferentiated and differentiated cells. Our results provide novel insights into the possible role of G6PC3 in the dephosphorylation of alternative sugar phosphates or their metabolites synthesized in the endoplasmic reticulum and confirm the potential feature of the enzyme in the promyelocytic stage as well. These findings contribute to our knowledge of intracellular carbohydrate metabolism of neutrophil granulocytes, which facilitates further research directions to better understand the underlying mechanisms of neutropenias.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 2","pages":"285-295"},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2 DDX3 通过对 PACT 的翻译控制以及与 AGO2 的相互作用，参与 miRNA 的生物发生和 RNA 干扰。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-14 DOI: 10.1002/2211-5463.13920

Ming-Chih Lai, Yen-Ling Yu, Chiao-Nung Chen, Jau-Song Yu, Hsin-Yuan Hung, Shih-Peng Chan

{"title":"DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2","authors":"Ming-Chih Lai, Yen-Ling Yu, Chiao-Nung Chen, Jau-Song Yu, Hsin-Yuan Hung, Shih-Peng Chan","doi":"10.1002/2211-5463.13920","DOIUrl":"10.1002/2211-5463.13920","url":null,"abstract":"DDX3 is a DEAD-box RNA helicase that plays multiple roles in RNA metabolism, including translation. We previously reported that DDX3 is required for translation of PACT, a binding partner of Dicer, suggesting a role for DDX3 in microRNA (miRNA) biogenesis and RNA interference (RNAi). Emerging evidence suggests that DDX3 plays a vital role in tumorigenesis and cancer progression, however, its underlying mechanism is still not fully understood. Here, we showed that the control of PACT by DDX3 is conserved in human cells and Caenorhabditis elegans. Using a miRNA microarray, we found that DDX3 regulates the expression of a small subset of cancer-related miRNAs. These oncogenic miRNAs were down-regulated by knockdown of DDX3 or PACT and up-regulated by overexpression of DDX3 or PACT in HEK293T cells. Similar results were obtained in human cancer HCT116 and HeLa cells. Dual luciferase reporter assay showed that DDX3 and PACT are required for short hairpin RNA (shRNA)-induced RNAi. We also performed co-immunoprecipitation to confirm the interaction between DDX3 and AGO2, a significant component of the RNA-induced silencing complex, supporting a role for DDX3 in the RNAi pathway. We further examined the effects of DDX3 and PACT on cell proliferation, and stable overexpression of DDX3 in HEK293 cells results in loss of contact inhibition of cell growth. Hence, we propose that DDX3 may participate in cancer development by regulating the RNAi pathway.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"180-195"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding and measuring mechanical signals in the tumor stroma. 了解和测量肿瘤基质中的机械信号。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-10 DOI: 10.1002/2211-5463.13923

Fàtima de la Jara Ortiz, Chiara Cimmino, Maurizio Ventre, Alessandra Cambi

引用次数: 0

Chorein deficiency promotes ferroptosis 胆囊素缺乏会促进铁蛋白沉积。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-08 DOI: 10.1002/2211-5463.13870

Yoshiaki Nishizawa, Hitoshi Sakimoto, Omi Nagata, Natsuki Sasaki, Yuka Urata, Kaoru Arai, Hanae Hiwatashi, Izumi Yokoyama, Shosei Kishida, Akira Sano, Masayuki Nakamura

{"title":"Chorein deficiency promotes ferroptosis","authors":"Yoshiaki Nishizawa, Hitoshi Sakimoto, Omi Nagata, Natsuki Sasaki, Yuka Urata, Kaoru Arai, Hanae Hiwatashi, Izumi Yokoyama, Shosei Kishida, Akira Sano, Masayuki Nakamura","doi":"10.1002/2211-5463.13870","DOIUrl":"10.1002/2211-5463.13870","url":null,"abstract":"Ferroptosis is a type of programmed cell death owed to an intracellular accumulation of iron resulting in the generation reactive oxygen species, which in turn can cause peroxidation of plasma membrane lipids and ultimately result in cell death. We investigated the potential involvement of VPS13A deficiency in ferroptosis. The VPS13A gene encodes for chorein, and its deficiency is a molecular cause of chorea-acanthocytosis (ChAc), a Huntington-like disease with neurodegeneration in the striatum. In our previous study, we found male infertility characterized by increased malondialdehyde staining of the spermatozoa in the testes of the ChAc model mice. Thus, in this study we performed metabolome analysis of sperm extracted from the epididymis of the ChAc model mice, which revealed decreased cystine levels, suggesting an association between chorein deficiency and ferroptosis. We then investigated the role of chorein in ferroptosis using VPS13A knockdown (VPS13A-KD) HEK293 cells. We found that VPS13A-KD cells displayed a significantly diminished resistance to tert-Butyl hydroperoxide (tBHP)-induced lipid peroxidation and cell death compared to control cells, which could be rescued by treatment with ferrostatin-1. Moreover, VPS13A-KD cells showed Fe(II) accumulation, suggesting an impaired capacity for divalent iron removal. In the cytosolic fraction of VPS13A-KD cells, the protein level of glutathione peroxidase 4 (GPX4) was significantly reduced, suggesting that dysfunction of chorein impairs GPX4 transport, thereby facilitating ferroptosis. These results suggest that ferroptosis may contribute to neurodegeneration in ChAc caused by loss of chorein function.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"58-68"},"PeriodicalIF":2.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

‘Let's work together to pass medical school’: a qualitative study of medical student attitudes to teamwork, competition and collaboration 让我们齐心协力，通过医学院的考试"：关于医学生对团队合作、竞争与协作态度的定性研究。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-07 DOI: 10.1002/2211-5463.13915

Helen R. Watson, Paul Millin, James Close, Robert Jeffery, Holly Stephenson, Daniel Zahra

{"title":"‘Let's work together to pass medical school’: a qualitative study of medical student attitudes to teamwork, competition and collaboration","authors":"Helen R. Watson, Paul Millin, James Close, Robert Jeffery, Holly Stephenson, Daniel Zahra","doi":"10.1002/2211-5463.13915","DOIUrl":"10.1002/2211-5463.13915","url":null,"abstract":"Teamwork is vital to all types of work, and graduates of higher education programmes must be prepared to contribute to a wide variety of professional teams. This is especially true in healthcare, where graduates will work in multidisciplinary teams (MDTs) under considerable pressure. This study is a follow-up to a previous study, where we described how competition between students is a barrier to constructive teamwork. Since then, we have made considerable enhancements to our transferable skills curriculum, moved away from norm referencing, and there have been national changes to the way that graduate Foundation training places are allocated. Here we present findings from a qualitative study of students from all six stages of our medical degree programme (5 years plus predegree foundation year). We explored whether there had been changes in how students perceived the importance of teamwork, their own teamwork development and how they collaborated with their peers. Following analysis of in-depth, semi-structured interviews, five themes emerged: (a) competition between students; (b) importance of teamwork; (c) what makes effective teamwork; (d) preparing for work in MDTs; and (e) recommendations for teamwork education. Competition between students was perceived as both positive and negative, but there has been a shift since our last study towards collaboration, with students now more willing to help each other succeed. Students also show more insight into their teamwork development, and were able to discuss what aspects of the programme, and higher education more broadly, were most valuable in helping them develop.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 2","pages":"359-372"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heat application in live cell imaging 活细胞成像中的热应用。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-03 DOI: 10.1002/2211-5463.13912

Linda Sistemich, Simon Ebbinghaus

引用次数: 0

Assessment IS learning: developing a student-centred approach for assessment in Higher Education 评估即学习：在高等教育中开发以学生为中心的评估方法。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-01 DOI: 10.1002/2211-5463.13921

Stephen Rutherford, Connie Pritchard, Nigel Francis

{"title":"Assessment IS learning: developing a student-centred approach for assessment in Higher Education","authors":"Stephen Rutherford, Connie Pritchard, Nigel Francis","doi":"10.1002/2211-5463.13921","DOIUrl":"10.1002/2211-5463.13921","url":null,"abstract":"Assessment and the associated feedback from those assessments are powerful factors in the development of students' learning. We have seen a shift within the Higher Education sector to conceptualise assessment as being more than summative assessment ‘of’ learning. Instead, there has been a greater emphasis on assessment ‘as’ learning, or assessment ‘for’ learning, through the enhanced use of formative assessments. Centralising assessment within the learning process highlights that assessment IS learning and cannot be separated from other elements of the learning process. In particular, assessment has a vital role to play in the development of students' self-regulated learning skills and the development of independence in learners. However, for assessments to effectively support learning, they need to be meaningful, engaging, well-integrated into the learning activities and ‘student-focused’. Placing student skills development and personal development at the centre of assessment design has the potential to empower students through assessment. This review focuses on the potential of assessment to support student learning and development, using the ‘Equity, Agency, Transparency’ (‘EAT’) framework as a lens for effective assessment and feedback practices. We suggest ways in which we can make our assessment and feedback practices more inclusive, meaningful and authentic to the students' learning needs.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"21-34"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RETRACTION: Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus 回归：Bach2的过度表达通过抑制系统性红斑狼疮中IRF4的表达来抑制Th9细胞的分化。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-11-01 DOI: 10.1002/2211-5463.13922

引用次数: 0

Proximity-dependent biotinylation reveals an interaction between ubiquitin-specific peptidase 46 and centrosome-related proteins 接近依赖性生物素化揭示了泛素特异性肽酶 46 与中心体相关蛋白之间的相互作用。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-10-31 DOI: 10.1002/2211-5463.13918

Kazuma Yoshioka, Reiko Nakagawa, Chi Lieu Kim Nguyen, Hayate Suzuki, Kiyohiro Ishigaki, Seiya Mizuno, Tsukasa Okiyoneda, Shizufumi Ebihara, Kazuya Murata

{"title":"Proximity-dependent biotinylation reveals an interaction between ubiquitin-specific peptidase 46 and centrosome-related proteins","authors":"Kazuma Yoshioka, Reiko Nakagawa, Chi Lieu Kim Nguyen, Hayate Suzuki, Kiyohiro Ishigaki, Seiya Mizuno, Tsukasa Okiyoneda, Shizufumi Ebihara, Kazuya Murata","doi":"10.1002/2211-5463.13918","DOIUrl":"10.1002/2211-5463.13918","url":null,"abstract":"Protein ubiquitination extensively modulates protein functions and controls various biological processes, such as protein degradation, signal transduction, transcription, and DNA repair. Ubiquitination is a reversible post-translational modification, and deubiquitinating enzymes cleave ubiquitin from proteins. Ubiquitin-specific peptidase 46 (USP46), a deubiquitinase, is highly expressed in the brain and regulates neural functions. Deleting lysine 92 (ΔK92) in USP46 reduces murine depression-like behavior in the tail suspension test. However, the molecular basis for USP46's role in regulating neural function has not yet been fully understood. Here we employed a proximity-dependent biotinylation approach to characterize the USP46 protein interaction partners. Using homology-independent targeted integration (HITI), a genome editing technique, we established knockin cell lines that stably express USP46 wildtype- or ΔK92-biotin ligase fusion protein. We identified 286 candidate interaction partners, including well-known binding partners of USP46. Although there were no obvious differences in the interactome of USP46 between wildtype and ΔK92, a gene ontology analysis revealed that centrosome-related proteins were significantly enriched in the proximal proteins of USP46. Several centrosome-related proteins were bound to USP46 in Neuro2a cells, but their protein expression levels were not affected in the brains of USP46-deficient mice. These results uncover a potential relationship between USP46 and centrosome regulation independently of protein stabilization.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"151-164"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects 赖氨酸去乙酰化酶抑制剂在细胞中的选择性较低，主要表现为脱靶效应。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2024-10-31 DOI: 10.1002/2211-5463.13896

Kiara E. Bornes, Marcus A. Moody, Thomas M. Huckaba, Megan C. Benz, Emily C. McConnell, Maryam Foroozesh, Van H. Barnes, Bridgette M. Collins-Burow, Matthew E. Burow, Terry J. Watt, Tasha B. Toro

{"title":"Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects","authors":"Kiara E. Bornes, Marcus A. Moody, Thomas M. Huckaba, Megan C. Benz, Emily C. McConnell, Maryam Foroozesh, Van H. Barnes, Bridgette M. Collins-Burow, Matthew E. Burow, Terry J. Watt, Tasha B. Toro","doi":"10.1002/2211-5463.13896","DOIUrl":"10.1002/2211-5463.13896","url":null,"abstract":"Lysine deacetylases (KDACs or HDACs) are metal-dependent enzymes that regulate lysine acetylation, a post-translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off-target binding, but the biological consequences of off-target binding were not evaluated. We compared the effects of treatment with two of the reportedly most KDAC-selective inhibitors, Tubastatin A and PCI-34051, in HT1080 cells in which the endogenous KDAC6 or KDAC8 gene has been mutated to inactivate enzyme catalysis while retaining enzyme expression. Genetic inactivation results in much stronger deacetylation defects on known targets compared to inhibitor treatment. Gene expression analysis revealed that both inhibitors have extensive and extensively overlapping off-target effects in cells, even at low inhibitor doses. Furthermore, Tubastatin A treatment led to increased histone acetylation, while inactivation of KDAC6 or KDAC8 did not. Genetic inactivation of KDAC6, but not KDAC8, impaired tumor formation in a xenograft model system, in contrast to previous reports with KDAC inhibitors suggesting the reverse. We conclude that the majority of observed biological effects of treatment with KDAC inhibitors are due to off-target effects rather than the intended KDAC inhibition. Developing a truly specific KDAC6 inhibitor could be a promising therapeutic avenue, but it is imperative to develop new inhibitors that selectively mimic genetic inactivation of individual KDACs.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"94-107"},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0