{"title":"Dynamic regulation of eEF1A1 acetylation affects colorectal carcinogenesis.","authors":"Hongpeng Jiang, Yu Zhang, Boya Liu, Xin Yang, Zhe Wang, Meng Han, Huiying Li, Jianyuan Luo, Hongwei Yao","doi":"10.1515/hsz-2022-0180","DOIUrl":"https://doi.org/10.1515/hsz-2022-0180","url":null,"abstract":"<p><p>The dysregulation of the translation elongation factor families which are responsible for reprogramming of mRNA translation has been shown to contribute to tumor progression. Here, we report that the acetylation of eukaryotic Elongation Factor 1 Alpha 1 (eEF1A1/EF1A1) is required for genotoxic stress response and maintaining the malignancy of colorectal cancer (CRC) cells. The evolutionarily conserved site K439 is identified as the key acetylation site. Tissue expression analysis demonstrates that the acetylation level of eEF1A1 K439 is higher than paired normal tissues. Most importantly, hyperacetylation of eEF1A1 at K439 negatively correlates with CRC patient survival. Mechanistically, CBP and SIRT1 are the major acetyltransferase and deacetylase of eEF1A1. Hyperacetylation of eEF1A1 at K439 shows a significant tumor-promoting effect by increasing the capacity of proliferation, migration, and invasion of CRC cells. Our findings identify the altered post-translational modification at the translation machines as a critical factor in stress response and susceptibility to colorectal carcinogenesis.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9859467","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}
{"title":"Small-molecule metabolites in SARS-CoV-2 treatment: a comprehensive review.","authors":"Reza Alipoor, Reza Ranjbar","doi":"10.1515/hsz-2022-0323","DOIUrl":"https://doi.org/10.1515/hsz-2022-0323","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread all over the world. In this respect, traditional medicinal chemistry, repurposing, and computational approaches have been exploited to develop novel medicines for treating this condition. The effectiveness of chemicals and testing methods in the identification of new promising therapies, and the extent of preparedness for future pandemics, have been further highly advantaged by recent breakthroughs in introducing noble small compounds for clinical testing purposes. Currently, numerous studies are developing small-molecule (SM) therapeutic products for inhibiting SARS-CoV-2 infection and replication, as well as managing the disease-related outcomes. Transmembrane serine protease (TMPRSS2)-inhibiting medicinal products can thus prevent the entry of the SARS-CoV-2 into the cells, and constrain its spreading along with the morbidity and mortality due to the coronavirus disease 2019 (COVID-19), particularly when co-administered with inhibitors such as chloroquine (CQ) and dihydroorotate dehydrogenase (DHODH). The present review demonstrates that the clinical-stage therapeutic agents, targeting additional viral proteins, might improve the effectiveness of COVID-19 treatment if applied as an adjuvant therapy side-by-side with RNA-dependent RNA polymerase (RdRp) inhibitors.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542732","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}
Simon L Wadle, Tatjana T X Schmitt, Jutta Engel, Simone Kurt, Jan J Hirtz
{"title":"Altered population activity and local tuning heterogeneity in auditory cortex of <i>Cacna2d3</i>-deficient mice.","authors":"Simon L Wadle, Tatjana T X Schmitt, Jutta Engel, Simone Kurt, Jan J Hirtz","doi":"10.1515/hsz-2022-0269","DOIUrl":"https://doi.org/10.1515/hsz-2022-0269","url":null,"abstract":"<p><p>The α<sub>2</sub>δ3 auxiliary subunit of voltage-activated calcium channels is required for normal synaptic transmission and precise temporal processing of sounds in the auditory brainstem. In mice its loss additionally leads to an inability to distinguish amplitude-modulated tones. Furthermore, loss of function of α<sub>2</sub>δ3 has been associated with autism spectrum disorder in humans. To investigate possible alterations of network activity in the higher-order auditory system in α<sub>2</sub>δ3 knockout mice, we analyzed neuronal activity patterns and topography of frequency tuning within networks of the auditory cortex (AC) using two-photon Ca<sup>2+</sup> imaging. Compared to wild-type mice we found distinct subfield-specific alterations in the primary auditory cortex, expressed in overall lower correlations between the network activity patterns in response to different sounds as well as lower reliability of these patterns upon repetitions of the same sound. Higher AC subfields did not display these alterations but showed a higher amount of well-tuned neurons along with lower local heterogeneity of the neurons' frequency tuning. Our results provide new insight into AC network activity alterations in an autism spectrum disorder-associated mouse model.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051526","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}
Chuang-Hong Lu, De-Xin Chen, Kun Dong, Yun-Jiao Wu, Na Na, Hong Wen, Yao-Shi Hu, Yuan-Ying Liang, Si-Yi Wu, Bei-You Lin, Feng Huang, Zhi-Yu Zeng
{"title":"Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis.","authors":"Chuang-Hong Lu, De-Xin Chen, Kun Dong, Yun-Jiao Wu, Na Na, Hong Wen, Yao-Shi Hu, Yuan-Ying Liang, Si-Yi Wu, Bei-You Lin, Feng Huang, Zhi-Yu Zeng","doi":"10.1515/hsz-2022-0334","DOIUrl":"https://doi.org/10.1515/hsz-2022-0334","url":null,"abstract":"<p><p>MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (<i>H</i>/<i>R</i>) models were built for clarifying the miR-143-3p's role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon <i>H</i>/<i>R</i>, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p's pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071376","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}
Biological ChemistryPub Date : 2023-05-22Print Date: 2023-07-26DOI: 10.1515/hsz-2023-0155
Ralph H Kehlenbach, Piotr Neumann, Ralf Ficner, Achim Dickmanns
{"title":"Interaction of nucleoporins with nuclear transport receptors: a structural perspective.","authors":"Ralph H Kehlenbach, Piotr Neumann, Ralf Ficner, Achim Dickmanns","doi":"10.1515/hsz-2023-0155","DOIUrl":"10.1515/hsz-2023-0155","url":null,"abstract":"<p><p>Soluble nuclear transport receptors and stationary nucleoporins are at the heart of the nucleocytoplasmic transport machinery. A subset of nucleoporins contains characteristic and repetitive FG (phenylalanine-glycine) motifs, which are the basis for the permeability barrier of the nuclear pore complex (NPC) that controls transport of macromolecules between the nucleus and the cytoplasm. FG-motifs can interact with each other and/or with transport receptors, mediating their translocation across the NPC. The molecular details of homotypic and heterotypic FG-interactions have been analyzed at the structural level. In this review, we focus on the interactions of nucleoporins with nuclear transport receptors. Besides the conventional FG-motifs as interaction spots, a thorough structural analysis led us to identify additional similar motifs at the binding interface between nucleoporins and transport receptors. A detailed analysis of all known human nucleoporins revealed a large number of such phenylalanine-containing motifs that are not buried in the predicted 3D-structure of the respective protein but constitute part of the solvent-accessible surface area. Only nucleoporins that are rich in conventional FG-repeats are also enriched for these motifs. This additional layer of potential low-affinity binding sites on nucleoporins for transport receptors may have a strong impact on the interaction of transport complexes with the nuclear pore and, thus, the efficiency of nucleocytoplasmic transport.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10529727","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}
Biological ChemistryPub Date : 2023-05-11Print Date: 2024-02-26DOI: 10.1515/hsz-2023-0108
Shunping Zhu, Bihong Liao
{"title":"Mechanism of hypoxia-induced exosome circ_0051799 regulating the progression of lung adenocarcinoma.","authors":"Shunping Zhu, Bihong Liao","doi":"10.1515/hsz-2023-0108","DOIUrl":"10.1515/hsz-2023-0108","url":null,"abstract":"<p><p>This study attempted to investigate the effect of circ_0051799 on the immune microenvironment of lung adenocarcinoma (LUAD) and the relationship between circ_0051799 and exosomes. The number and morphology of exosomes were verified by nanoparticle tracking, transmission electron microscopy and western blotting. CCK8, EdU, Transwell and flow cytometry were used to verify the regulatory role of exosomes and circ_0051799 on tumor progression. Dual luciferase reporting and RNA immunoprecipitation were used to verify the targeted regulatory relationship between circ_0051799, miR-214-3p and IGF2BP3. WB was used to verify the role of the JAK/STAT pathway in circ_0051799 regulation. Ectopic tumor grafts and <i>in situ</i> models were used to validate <i>in vivo</i> their role in regulating LUAD progression. Hypoxic environment could alter but does not alter its shape. Exosomes can participate in the regulation of macrophage polarization by circ_0051799. <i>In vitro</i> and <i>in vivo</i> assays had shown that circ_0051799 could affect the proliferation and metastasis of LUAD through targeting miR-214-3p mediated IGF2BP3 regulated JAK/STAT pathway. This study found that hypoxia can affect LUAD process by promoting the regulation of macrophage polarization by exosome circ_0051799.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444203","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}
Biological ChemistryPub Date : 2023-05-09Print Date: 2023-07-26DOI: 10.1515/hsz-2023-0133
Abhijith Makki, Peter Rehling
{"title":"Protein transport along the presequence pathway.","authors":"Abhijith Makki, Peter Rehling","doi":"10.1515/hsz-2023-0133","DOIUrl":"10.1515/hsz-2023-0133","url":null,"abstract":"<p><p>Most mitochondrial proteins are nuclear-encoded and imported by the protein import machinery based on specific targeting signals. The proteins that carry an amino-terminal targeting signal (presequence) are imported via the presequence import pathway that involves the translocases of the outer and inner membranes - TOM and TIM23 complexes. In this article, we discuss how mitochondrial matrix and inner membrane precursor proteins are imported along the presequence pathway in <i>Saccharomyces cerevisiae</i> with a focus on the dynamics of the TIM23 complex, and further update with some of the key findings that advanced the field in the last few years.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185684","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}
Biological ChemistryPub Date : 2023-05-05Print Date: 2023-07-26DOI: 10.1515/hsz-2023-0126
Lisa Marquardt, Michael Thumm
{"title":"Autophagic and non-autophagic functions of the <i>Saccharomyces cerevisiae</i> PROPPINs Atg18, Atg21 and Hsv2.","authors":"Lisa Marquardt, Michael Thumm","doi":"10.1515/hsz-2023-0126","DOIUrl":"10.1515/hsz-2023-0126","url":null,"abstract":"<p><p>Atg18, Atg21 and Hsv2 are homologous β-propeller proteins binding to PI3P and PI(3,5)P<sub>2</sub>. Atg18 is thought to organize lipid transferring protein complexes at contact sites of the growing autophagosome (phagophore) with both the ER and the vacuole. Atg21 is restricted to the vacuole phagophore contact, where it organizes part of the Atg8-lipidation machinery. The role of Hsv2 is less understood, it partly affects micronucleophagy. Atg18 is further involved in regulation of PI(3,5)P<sub>2</sub> synthesis. Recently, a novel Atg18-retromer complex and its role in vacuole homeostasis and membrane fission was uncovered.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536733","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}
{"title":"<i>Drosophila</i> collagens in specialised extracellular matrices.","authors":"Marcel Reinhardt, Maik Drechsler, Achim Paululat","doi":"10.1515/hsz-2022-0297","DOIUrl":"https://doi.org/10.1515/hsz-2022-0297","url":null,"abstract":"<p><p>The basement membrane (BM) constitutes a specialised form of the extracellular matrix (ECM) and plays important roles in many biological processes, such as cell migration, organ and tissue integrity, cell polarity, and the formation of metastases. In metazoans, a canonical BM is formed by only a few conserved structural core proteins: Laminin, Collagen IV, Nidogen and Perlecan. Depending on the tissue's function and mechanical load, additional matrix proteins interact with, or are incorporated into the BM, resulting in tissue-specific mechanical properties, such as higher stiffness or elasticity, or special resistance to mechanical stress or harmful environmental conditions. In flies, the collagen IV-like protein Pericardin forms an integral constituent of matrices around the heart and tension sensors (chordotonal organs) of the peripheral nervous system. The function and integrity of both organ systems strongly relies on the appropriate establishment of a Pericardin (Prc) matrix and the function of its adapter protein-Lonely heart (Loh). In this review, we provide an overview of the four collagens present in flies, and will discuss our recent work on the formation and function of Pericardin-containing matrices, the role of the adapter protein Lonely heart and the necessity of specialised ECM molecules in tissue architecture and function.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9312886","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}