Biochemistry and Biophysics Reports最新文献

{"title":"LINC01322 may serve as a potential diagnostic marker for advanced stage tumors in renal cell carcinoma patients eligible for total nephrectomy","authors":"Amirhosein Maharati ,&nbsp;Negin Taghehchian ,&nbsp;Fatemeh Taghavinia ,&nbsp;Alireza Golshan ,&nbsp;Azadeh Aarabi ,&nbsp;Mohammad Reza Abbaszadegan ,&nbsp;Meysam Moghbeli","doi":"10.1016/j.bbrep.2024.101843","DOIUrl":"10.1016/j.bbrep.2024.101843","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC) is a common urological cancer globally and shows a favorable prognosis in early stages of the tumor progression. Due to the poor prognosis for metastatic RCC patients, it is crucial to explore the molecular biology of RCC progression to establish efficient diagnostic and therapeutic markers for these patients. Long non-coding RNAs (lncRNAs) have critical roles in regulation of tumor cell proliferation, migration, and apoptosis during RCC progression. For the first time in the present study, we assessed the LINC01322 RNA expression levels in RCC patients to introduce that as a potential tumor marker among these patients.</div></div><div><h3>Methods</h3><div>we visualized LINC01322 expression data using the online tool Gene Expression Profiling Interactive Analysis (GEPIA2) across different cancers and normal tissues. Fifty fresh samples of RCC tumor tissues and their adjacent normal margins were collected to analyze the RNA expression of LINC01322 and its association with the clinicopathological features of RCC patients. The SYBR green method was used in real-time PCR to measure the LINC01322 RNA expression levels in RCC patients.</div></div><div><h3>Results</h3><div>Based on in-silico analysis, we hypothesized that LINC01322 could be involved in RCC progression by interacting with VHL, thereby influencing the tumor microenvironment. There were significant increased levels of LINC01322 RNA expressions in advanced stage compared with primary stage tumors that were located in left kidney (p = 0.048). Left kidney that were undergone the total nephrectomy had significant higher levels of LINC01322 RNA expressions compared with tumors in right kidney (p = 0.045). There was a direct correlation between the levels of LINC01322 RNA expression and RCC tumor size.</div></div><div><h3>Conclusions</h3><div>considering the substantial increase in LINC01322 RNA expression in advanced stage RCC tumors that are candidates for total nephrectomy; it could be suggested as a potential diagnostic indicator for high-risk patients. In-silico analysis also revealed that LINC01322 could be involved in regulation of tumor microenvironment during RCC progression by interacting with VHL. However, further investigations are needed to validate the potential link between LINC01322 and VHL during RCC progression. Evaluating the serum LINC01322 RNA levels in RCC patients is also necessary to use that as a diagnostic marker in clinical settings.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Label-based comparative proteomics of oral mucosal tissue to understand progression of precancerous lesions to oral squamous cell carcinoma","authors":"Vipra Sharma ,&nbsp;Sundararajan Baskar Singh ,&nbsp;Sabyasachi Bandyopadhyay ,&nbsp;Kapil Sikka ,&nbsp;Aanchal Kakkar ,&nbsp;Gururao Hariprasad","doi":"10.1016/j.bbrep.2024.101842","DOIUrl":"10.1016/j.bbrep.2024.101842","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Oral squamous cell carcinomas typically arise from precancerous lesions such as leukoplakia and erythroplakia. These lesions exhibit a range of histological changes from hyperplasia to dysplasia and carcinoma in situ, during their transformation to malignancy. The molecular mechanisms driving this multistage transition remain incompletely understood. To bridge this knowledge gap, our current study utilizes label based comparative proteomics to compare protein expression profiles across different histopathological grades of leukoplakia, erythroplakia, and oral squamous cell carcinoma samples, aiming to elucidate the molecular changes underlying lesion evolution.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methodology&lt;/h3&gt;&lt;div&gt;An 8-plex iTRAQ proteomics of 4 biological replicates from 8 clinical phenotypes of leukoplakia and erythroplakia, with hyperplasia, mild dysplasia, moderate dysplasia; along with phenotypes of well differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma was carried out using the Orbitrap Fusion Lumos mass spectrometer. Raw files were processed with Maxquant, and statistical analysis across groups was conducted using MetaboAnalyst. Statistical tools such as ANOVA, PLS-DA VIP scoring, and correlation analysis were employed to identify differentially expressed proteins that had a linear expression variation across phenotypes of hyperplasia to cancer. Validation was done using Bioinformatic tools such as ClueGO + Cluepedia plugin in Cytoscape to extract functional annotations from gene ontology and pathway databases.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results and discussion&lt;/h3&gt;&lt;div&gt;A total of 2685 protein groups and 12,397 unique peptides were identified, and 61 proteins consistently exhibited valid reporter ion corrected intensities across all samples. Of these, 6 proteins showed linear varying expression across the analysed sample phenotypes. Collagen type VI alpha 2 chain (COL6A2), Fibrinogen β chain (FGB), and Vimentin (VIM) were found to have increased linear expression across pre-cancer phenotypes of leukoplakia to cancer, while Annexin A7 (ANXA7) was seen to be having a linear decreasing expression. Collagen type VI alpha 2 chain (COL6A2) and Annexin A2 (ANXA2) had increased linear expression across precancer phenotypes of erythroplakia to cancer. The mass spectrometry proteomics data have been deposited to the ProteomeXchanger Consortium via the PRIDE partner repository with the data set identifier PXD054190. These differentially expressed proteins mediate cancer progression mainly through extracellular exosome; collagen-containing extracellular matrix, hemostasis, platelet aggregation, and cell adhesion molecule binding.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Label-based proteomics is an ideal platform to study oral cancer progression. The differentially expressed proteins provide insights into the molecular mechanisms underlying the progression of oral premalignant lesions to malignant ph","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of arginine kinase proteins: What we need to know?","authors":"Brenda Martins Vasconcellos ,&nbsp;Victor Guimarães Ribeiro ,&nbsp;Naysha do Nascimento Campos ,&nbsp;Luis Guilherme da Silva Romão Mota ,&nbsp;Mônica Ferreira Moreira","doi":"10.1016/j.bbrep.2024.101837","DOIUrl":"10.1016/j.bbrep.2024.101837","url":null,"abstract":"<div><div>The enzyme arginine kinase (AK), EC 2.7.3.3, catalyzes the reversible phosphorylation of arginine with adenosine triphosphate, forming phosphoarginine, which acts as an energy reservoir due to its high-energy phosphate content that can be rapidly transferred to ADP for ATP renewal. It has been proposed that AK should be associated with some ATP biosynthesis mechanisms, such as glycolysis and oxidative phosphorylation. Arginine kinase is an analogue of creatine kinase found in vertebrates. A literature survey has recovered the physicochemical and structural characteristics of AK. This enzyme is widely distributed in invertebrates such as protozoa, bacteria, porifera, cnidaria, mollusca, and arthropods. Arginine kinase may be involved in the response to abiotic and biotic stresses, being up regulated in several organisms and controlling energy homeostasis during environmental changes. Additionally, phosphoarginine plays a role in providing energy for the transport of protozoa, the beating of cilia, and flagellar movement, processes that demand continuous energy. Arginine kinase is also associated with allergies to shellfish and arthropods, such as shrimp, oysters, and cockroaches. Phenolic compounds such as resveratrol, which decrease AK activity by 50 % in <em>Trypanosoma cruzi,</em> inhibit the growth of the epimastigote and trypomastigote forms, making them a significant target for the development of medications for Chagas Disease treatment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercise improved the hematological effect of vitamin D in type 2 diabetes mellitus-induced nephrotoxicity in rats","authors":"Halimat Amin Abdulrahim ,&nbsp;Adeyemi Fatai Odetayo ,&nbsp;Adeoye Tunwagun David ,&nbsp;Yusuf Funsho Abdulquadri ,&nbsp;Rofiat Oluwasheun Sheu ,&nbsp;Pelumi Kikelomo Oluwafemi ,&nbsp;Kazeem Bidemi Okesina ,&nbsp;Luqman Aribidesi Olayaki","doi":"10.1016/j.bbrep.2024.101839","DOIUrl":"10.1016/j.bbrep.2024.101839","url":null,"abstract":"<div><h3>Introduction</h3><div>Globally, one of the major causes of renal dysfunction is diabetes mellitus (DM), and diabetic-induced nephrotoxicity has been linked with anemia. Presently, numerous antidiabetic drugs have been designed for the management of this disorder but they possess their undesirable effects such as anemia and acute kidney injury. Hence, we explore the use of vitamin D with or without exercise for the management of DM-induced renal dysfunction.</div></div><div><h3>Methods</h3><div>Thirty-six (36) Wistar rats were randomly separated into six (6) groups: control (vehicle treated), diabetes untreated (HFD + STZ), diabetes + vitamin D (HFD + STZ + vitamin D), diabetes + exercise (HFD + STZ + exercise), diabetes + vitamin D + exercise (HFD + STZ + vitamin D+ exercise), diabetes + metformin (HFD + STZ + metformin).</div></div><div><h3>Results</h3><div>Vitamin D with or without exercise significantly reduced T2DM-induced hyperglycemia. Also, a decrease in T2DM-induced increase in urea, creatinine, lactate dehydrogenase, lactate, cholesterol, and triglyceride and a rise in DM-associated reduction in high-density lipoprotein. These events were associated with a significant increase in red blood cells, hematocrit value, hemoglobin, erythropoietin, and a decrease in white blood cell count. Furthermore, vitamin D with or without exercise reversed T2DM-induced increase in pro-oxidant and pro-inflammatory markers. This observed oxido-inflammatory response was associated with a significant increase in xanthine oxidase activities and uric acid concentration. Interestingly, better recovery rates from DM-associated hematological imbalance were discovered in rats co-treated with vitamin D and exercise.</div></div><div><h3>Conclusion</h3><div>Our findings revealed that exercise enhanced the hematological effect of vitamin D in HFD + STZ-induced T2DM animals.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics of three different α-helices in ribosomal protein L25 from Escherichia coli","authors":"Yuri Chirgadze ,&nbsp;Ilya Likhachev ,&nbsp;Nikolai Balabaev ,&nbsp;Evgeniy Brazhnikov","doi":"10.1016/j.bbrep.2024.101836","DOIUrl":"10.1016/j.bbrep.2024.101836","url":null,"abstract":"<div><div>A true native protein state is realized in a water solution where proteins exhibit their dynamic properties important for the functioning. This is way we have analyzed the dynamics of α-helices inside ribosomal protein L25 from <em>Escherichia coli</em> in a water solution. The dynamics of only main chain Cα-atoms have been simulated along the five independent trajectories at a total time 200ns. Superposed average dynamics picture of L25 structure coincides very well with the NMR protein structure in a water solution. Dynamic shifts of Cα-atoms of the α-helices are related with a restraint status of the residue side chain. In contrast, Cα-atoms of the β-sheet, which form a hydrophobic core, show very low dynamic motion and higher stability. Dynamic specificity of the main chain of protein L25 could explain its particular features in the complex with 5S rRNA and in the structure of the ribosome.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lutein and zeaxanthin reduce neuronal cell damage caused by lipid peroxidation","authors":"Satoshi Morita,&nbsp;Toshiaki Sueyasu,&nbsp;Hisanori Tokuda,&nbsp;Yoshihisa Kaneda,&nbsp;Takayuki Izumo,&nbsp;Yoshihiro Nakao","doi":"10.1016/j.bbrep.2024.101835","DOIUrl":"10.1016/j.bbrep.2024.101835","url":null,"abstract":"<div><div>Oxidative stress and lipid peroxide levels in the brain increase with aging. The carotenoids lutein and zeaxanthin have potent antioxidant properties and the ability to improve cognitive function. However, their effects on neuronal damage <em>via</em> lipid peroxidation remain unknown. Therefore, we aimed to elucidate the effects of these carotenoids on neuronal damage induced by accumulated peroxidized lipids. We developed an oxidative stress model of lipid peroxidation-induced neuronal damage using differentiated neuronal cells derived from human neuroblastoma SH-SY5Y cells <em>in vitro</em>. Combining rotenone and RSL3 increased mitochondrial oxidative stress and lipid reactive oxygen species (ROS), which resulted in enhanced neuronal damage. Lutein and zeaxanthin were added to the cells for 1 week, and these carotenoids suppressed mitochondrial oxidative stress and lipid peroxidation in differentiated neuronal cells and mitigated neuronal damage. Further investigation is required to clarify the underlying pathways in detail.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dose-effect response of combined red and infrared photobiomodulation on insulin resistance in skeletal muscle cells","authors":"Gabriela Silva ,&nbsp;Saulo Soares da Silva ,&nbsp;Dimitrius Santiago Passos Simões Fróes Guimarães ,&nbsp;Marcos Vinicius da Cruz ,&nbsp;Leonardo Reis Silveira ,&nbsp;Etel Rocha-Vieira ,&nbsp;Fabiano Trigueiro Amorim ,&nbsp;Flavio de Castro Magalhaes","doi":"10.1016/j.bbrep.2024.101831","DOIUrl":"10.1016/j.bbrep.2024.101831","url":null,"abstract":"<div><div>Obesity is a major public health problem and is a major contributor to the development of insulin resistance. In previous studies we observed that single-wavelength red or infrared photobiomodulation (PBM) improved insulin signaling in adipocytes and skeletal muscle of mice fed a high-fat diet, but information about the combination of different wavelengths, as well as the effect of different light doses (J/cm²) is lacking. Therefore, the aim of this study was to investigate the effects of different doses of dual-wavelength PBM on insulin signaling in muscle cell, and explore potential mechanisms involved. Mouse myoblasts (C2C12) were differentiated into myotubes and cultured in palmitic acid, sodium oleate and <span>l</span>-carnitine (PAL) to induce insulin resistance high or in glucose medium (CTRL). Then, they received SHAM treatment (lights off, 0 J/cm²) or PBM (660 + 850 nm; 2, 4 or 8 J/cm²). PAL induced insulin resistance (assessed by Akt phosphorylation at ser473), attenuated maximal citrate synthase activity, and increased the phosphorylation of c-Jun NH(2) terminal kinase (JNK) (T183/Y185). PBM at doses of 4 or 8 J/cm² reversed these PAL-induced responses. Furthermore, at doses of 2, 4 or 8 J/cm², PBM reversed the increase in mitofusin-2 content induced by PAL. In conclusion, the combination of dual-wavelength red and infrared PBM at doses of 4 and 8 J/cm² improved intracellular insulin signaling in musculoskeletal cells, and this effect appears to involve the modulation of mitochondrial function and the attenuation of the activation of stress kinases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer","authors":"Jie Yu ,&nbsp;Wenke Cai ,&nbsp;Tao Zhou ,&nbsp;Bo Men ,&nbsp;Shunqiong Chen ,&nbsp;Dong Tu ,&nbsp;Wei Guo ,&nbsp;Jicui Wang ,&nbsp;Feipeng Zhao ,&nbsp;Yan Wang","doi":"10.1016/j.bbrep.2024.101833","DOIUrl":"10.1016/j.bbrep.2024.101833","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC.</div></div><div><h3>Methods</h3><div>A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF–κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay.</div></div><div><h3>Results</h3><div>CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF–κB pathway and, therefore, promote lymphangiogenesis.</div></div><div><h3>Conclusion</h3><div>We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of the Rho GTPases Cdc42, Rac1 or RhoA reduces PDGF-induced STAT1 and STAT3 signaling","authors":"Erik Wåhlén,&nbsp;Johan Lennartsson ,&nbsp;Johan Heldin","doi":"10.1016/j.bbrep.2024.101828","DOIUrl":"10.1016/j.bbrep.2024.101828","url":null,"abstract":"<div><div>This study investigates the role of Rho GTPases, specifically Cdc42, Rac1, and RhoA, in platelet-derived growth factor receptors (PDGFRα and PDGFRβ) signaling. Signal transducer and activator of transcription (STAT) proteins, essential for cellular processes such as proliferation and immune response, are activated downstream of PDGFRs. Dysregulation of these pathways is linked to various diseases, including cancer. The current study examines the effects of Rho GTPase depletion on PDGFR phosphorylation, STAT protein stability, and downstream signaling. Results indicate that depletion of Cdc42, Rac1, or RhoA impairs PDGFR phosphorylation and reduces STAT1 and STAT3 signaling, without significantly affecting AKT and ERK1/2 pathways. The findings highlight the critical regulatory roles of Rho GTPases in PDGFR-mediated STAT signaling.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthricin-induced hyperactive proteasome and its molecular mechanism","authors":"Kotaro Sakamoto ,&nbsp;Runa Fujimoto ,&nbsp;Erina Kamiyama-Ando ,&nbsp;Takatsugu Hirokawa","doi":"10.1016/j.bbrep.2024.101830","DOIUrl":"10.1016/j.bbrep.2024.101830","url":null,"abstract":"<div><div>Recently, targeted protein degradation has attracted increasing interest as a new drug discovery approach. This method aims to control the function of drug targets by inducing their degradation through protein degradation systems such as the proteasome. Concurrently, compounds that enhance proteasome activity have also garnered attention. In 2023, we reported that anthricin (also known as 4-deoxypodophyllotoxin), a natural product that belongs to the lignan family, enhances proteasome activity. However, whether this enhancement was because of increased proteasome expression or improved proteasome function remains unclear. In this study, we investigated the structure–activity relationship of anthricin and its analogs in enhancing proteasome activity, the effects of anthricin on proteasome-related gene expression, and the direct binding between anthricin and the proteasome using pull-down assay. Moreover, we assessed the interaction between anthricin and the proteasome using molecular dynamics (MD) simulations. The results showed that anthricin does not induce proteasome-related gene expression, but instead binds to the β-subunit of the proteasome, bringing the side chains of three amino acid residues (Thr¹, Asp¹⁷, and Lys³³) at the catalytic site closer together, thereby inducing a hyperactive state. To the best of our knowledge, this study is the first to suggest the mechanism of proteasome activity enhancement by anthricin at the molecular level. The findings could contribute to the development of new chemotypes to enhance the effects of targeted protein degraders by regulating proteasome activity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001948/pdfft?md5=343c70f733b5a3b299d119af0b30f2b1&pid=1-s2.0-S2405580824001948-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}