Biochimica et biophysica acta. General subjects最新文献

{"title":"Systemic and strict regulation of the glutathione redox state in mitochondria and cytosol is needed for zebrafish ontogeny","authors":"Kristin Hamre ,&nbsp;Wuxiao Zhang ,&nbsp;Maren Hoff Austgulen ,&nbsp;Eva Mykkeltvedt ,&nbsp;Peng Yin ,&nbsp;Marc Berntssen ,&nbsp;Marit Espe ,&nbsp;Carsten Berndt","doi":"10.1016/j.bbagen.2024.130603","DOIUrl":"10.1016/j.bbagen.2024.130603","url":null,"abstract":"<div><h3>Background</h3><p>Redox control seems to be indispensable for proper embryonic development. The ratio between glutathione (GSH) and its oxidized disulfide (GSSG) is the most abundant cellular redox circuit.</p></div><div><h3>Methods</h3><p>We used zebrafish harboring the glutaredoxin 1-redox sensitive green fluorescent protein (Grx1-roGFP) probe either in mitochondria or cytosol to test the hypothesis that the GSH:GSSG ratio is strictly regulated through zebrafish embryogenesis to sustain the different developmental processes of the embryo.</p></div><div><h3>Results</h3><p>Following the GSSG:GSH ratio as a proxy for the GSH-dependent reduction potential (E_{<em>h</em>GSH}) revealed increasing mitochondrial and cytosolic E_{<em>h</em>GSH} during cleavage and gastrulation. During organogenesis, cytosolic E_{<em>h</em>GSH} decreased, while that of mitochondria remained high. The similarity between E_{<em>h</em>GSH} in brain and muscle suggests a central regulation. Modulation of GSH metabolism had only modest effects on the GSSG:GSH ratios of newly hatched larvae. However, inhibition of GSH reductase directly after fertilization led to dead embryos already 10 h later. Exposure to the emerging environmental pollutant Perfluorooctane Sulfonate (PFOS) disturbed the apparent regulated E_{<em>h</em>GSH} as well.</p></div><div><h3>Conclusions</h3><p>Mitochondrial and cytosolic GSSG:GSH ratios are almost identical in different organs during zebrafish development indicating that the E_{<em>h</em>GSH} might follow H₂O₂ levels and rather indirectly affect specific enzymatic activities needed for proper embryogenesis.</p></div><div><h3>General significance</h3><p>Our data confirm that vertebrate embryogenesis depends on strictly regulated redox homeostasis. Disturbance of the GSSG:GSH circuit, e.g. induced by environmental pollution, leads to malformation and death.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decitabine combined with cold atmospheric plasma induces pyroptosis via the ROS/Caspase-3/GSDME signaling pathway in Ovcar5 cells","authors":"Liang Du ,&nbsp;Huiyun Ming ,&nbsp;Zhuna Yan ,&nbsp;Jinwu Chen ,&nbsp;Wencheng Song ,&nbsp;Haiming Dai","doi":"10.1016/j.bbagen.2024.130602","DOIUrl":"10.1016/j.bbagen.2024.130602","url":null,"abstract":"<div><h3>Background</h3><p>High methylation of the <em>DFNA5</em> gene results in the absence of GSDME, a key protein that mediates pyroptosis, while decitabine demethylates the <em>DFNA5</em> gene, resulting in high expression of the GSDME protein. Cold atmospheric plasma (CAP) is a novel anti-cancer method that induces tumor cell death.</p></div><div><h3>Methods</h3><p>The pyroptosis induced by decitabine in combination with CAP in Ovcar5 cells was evaluated. In particular, mitochondrial membrane potential was estimated by JC-1 staining, dehydrogenase (LDH) release was assessed by ELISA, Annexin V/PI staining was detected by flow cytometry, the cell cycle changes were evaluated using PI staining followed by detection by flow cytometry, and Caspase-9 cleavage, Caspase-3 cleavage and GSDME expression were evaluated by western blot.</p></div><div><h3>Results</h3><p>Decitabine resulted in high expression of the GSDME in Ovcar5 in a concentration-dependent manner and increased tumor cell sensitivity to CAP. CAP induced mitochondrial damage and activated the Caspase-9/Caspase-3 pathway. Therefore, decitabine combined with CAP induced Ovcar5 cell pyroptosis through Caspase-3 mediated GSDME cleavage. Reactive oxygen species (ROS) generated by CAP treatment played an important role in the CAP/decitabine combination-induced production of ROS, activation of Caspase-9/Caspase-3, GSDME cleavage and pyroptosis that ROS scavenger NAC inhibited all these processes.</p></div><div><h3>Conclusions</h3><p>CAP combined with decitabine induced Caspase-3 activation, which cleaved decitabine-upregulated GSDME and ediated pyroptosis.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-specificity tyrosine-regulated kinase 2 exerts anti-tumor effects by induction of G1 arrest in lung adenocarcinoma","authors":"Eriko Harada ,&nbsp;Saishu Yoshida ,&nbsp;Yuta Imaizumi ,&nbsp;Akira Kawamura ,&nbsp;Takashi Ohtsuka ,&nbsp;Kiyotsugu Yoshida","doi":"10.1016/j.bbagen.2024.130600","DOIUrl":"10.1016/j.bbagen.2024.130600","url":null,"abstract":"<div><h3>Objectives</h3><p>Lung cancer is a leading cause of cancer-related mortality and remains one of the most poorly prognosed disease worldwide. Therefore, it is necessary to identify novel molecular markers with potential therapeutic effects. Recent findings have suggested that dual-specificity tyrosine-regulated kinase 2 (DYRK2) plays a tumor suppressive role in colorectal, breast, and hepatic cancers; however, its effect and mechanism in lung cancer remain poorly understood. Therefore, this study aimed to investigate the tumor-suppressive role and molecular mechanism of DYRK2 in lung adenocarcinoma (LUAD) by <em>in vitro</em> experiments and xenograft models.</p></div><div><h3>Materials and methods</h3><p>The evaluation of DYRK2 expression was carried out using lung cancer cell lines and normal bronchial epithelial cells. Overexpression of DYRK2 was induced by an adenovirus vector, and cell proliferation was assessed through MTS assay and Colony Formation Assay. Cell cycle analysis was performed using flow cytometry. Additionally, proliferative capacity was evaluated in a xenograft model by subcutaneously implanting A549 cells into SCID mice (C·B17/Icr-scidjcl-scid/scid).</p></div><div><h3>Results</h3><p>Immunoblotting assays showed that DYRK2 was downregulated in most LUAD cell lines. DYRK2 overexpression using adenovirus vectors significantly suppressed cell proliferation compared with that in the control group. Additionally, DYRK2 overexpression suppressed tumor growth in a murine subcutaneous xenograft model. Mechanistically, DYRK2 overexpression inhibited the proliferation of LUAD cells <em>via</em> p21-mediated G1 arrest, which was contingent on p53.</p></div><div><h3>Conclusion</h3><p>Taken together, these findings suggest that DYRK2 may serve as potential prognostic biomarker and therapeutic target for LUAD.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a secreted aminopeptidase of M28 family from B. fragilis and its possible role in protein metabolism in the gut","authors":"Bhushan S. Kulkarni ,&nbsp;Ravindra D. Makde ,&nbsp;Sahayog N. Jamdar","doi":"10.1016/j.bbagen.2024.130598","DOIUrl":"10.1016/j.bbagen.2024.130598","url":null,"abstract":"<div><p>Products of microbial protein metabolism in the gut can influence the health of the host in many ways. Members of the Bacteriodales, major commensals of the human colon have been associated with long-term intake of high-protein diets. Undigested proteins or peptides that reach the colon can be hydrolyzed by extra-cellular proteases found in some <em>Bacteroides</em> species into amino acids and peptides which can be further catabolized. In this communication, we have characterized one such secreted aminopeptidase (BfAP) from <em>Bacteroides fragilis</em> belonging to the M28 family which is capable of degrading peptides released from soybean protein after predigestion in the small intestine. The BfAP enzyme was cloned, expressed in <em>E. coli</em>, and purified to homogeneity. It is a metallopeptidase requiring Co²⁺ ion for optimum activity at 55 °C and pH 8 and preferentially cleaves neutral aliphatic (Met/Leu) and positively charged (Arg/Lys) amino acids from the N-terminus of peptides. It showed high specificity for long peptides as well as proteins like β-casein. Structural analysis of BfAP and its orthologues using AlphaFold2 reveal a shared highly conserved M28 domain, but vary with respect to their N-terminal region with some of them possessing an additional cap domain which may be important for regulation of substrate binding. Although BfAP lacks the typical cap domain, it shows small extensions that can form a loop adjacent to the proposed active site and may affect substrate binding. We suggest that this secreted enzyme may play an important role in protein metabolism in the colon where <em>Bacteroides</em> species are abundant.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ASPTF: A computational tool to predict abiotic stress-responsive transcription factors in plants by employing machine learning algorithms","authors":"Upendra Kumar Pradhan ,&nbsp;Anuradha Mahapatra ,&nbsp;Sanchita Naha ,&nbsp;Ajit Gupta ,&nbsp;Rajender Parsad ,&nbsp;Vijay Gahlaut ,&nbsp;Surya Narayan Rath ,&nbsp;Prabina Kumar Meher","doi":"10.1016/j.bbagen.2024.130597","DOIUrl":"10.1016/j.bbagen.2024.130597","url":null,"abstract":"<div><h3>Background</h3><p>Abiotic stresses pose serious threat to the growth and yield of crop plants. Several studies suggest that in plants, transcription factors (TFs) are important regulators of gene expression, especially when it comes to coping with abiotic stresses. Therefore, it is crucial to identify TFs associated with abiotic stress response for breeding of abiotic stress tolerant crop cultivars.</p></div><div><h3>Methods</h3><p>Based on a machine learning framework, a computational model was envisaged to predict TFs associated with abiotic stress response in plants. To numerically encode TF sequences, four distinct sequence derived features were generated. The prediction was performed using ten shallow learning and four deep learning algorithms. For prediction using more pertinent and informative features, feature selection techniques were also employed.</p></div><div><h3>Results</h3><p>Using the features chosen by the light-gradient boosting machine-variable importance measure (LGBM-VIM), the LGBM achieved the highest cross-validation performance metrics (accuracy: 86.81%, auROC: 92.98%, and auPRC: 94.03%). Further evaluation of the proposed model (LGBM prediction method + LGBM-VIM selected features) was also done using an independent test dataset, where the accuracy, auROC and auPRC were observed 81.98%, 90.65% and 91.30%, respectively.</p></div><div><h3>Conclusions</h3><p>To facilitate the adoption of the proposed strategy by users, the approach was implemented as a prediction server called ASPTF, accessible at <span>https://iasri-sg.icar.gov.in/asptf/</span><svg><path></path></svg>. The developed approach and the corresponding web application are anticipated to supplement experimental methods in the identification of transcription factors (TFs) responsive to abiotic stress in plants.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative epigenome-transcriptome analysis unravels cancer-specific over-expressed genes potentially regulating immune microenvironment in clear cell renal cell carcinoma","authors":"Nikhil Gadewal ,&nbsp;Abhiram Natu ,&nbsp;Siddhartha Sen ,&nbsp;Sukanya Rauniyar ,&nbsp;Virupaksha Bastikar ,&nbsp;Sanjay Gupta","doi":"10.1016/j.bbagen.2024.130596","DOIUrl":"10.1016/j.bbagen.2024.130596","url":null,"abstract":"<div><h3>Background</h3><p>Clear cell Renal Cell Carcinoma (ccRCC) is the frequently diagnosed histological life-threatening tumor subtype in the urinary system. Integrating multi-omics data is emerging as a tool to provide a comprehensive view of biology and disease for better therapeutic interventions.</p></div><div><h3>Method</h3><p>We have integrated freely available ccRCC data sets of genome-wide DNA methylome, transcriptome, and active histone modification marks, H3K27ac, H3K4me1, and H3K4me3 specific ChIP-seq data to screen genes with higher expression. Further, these genes were filtered based on their effect on survival upon alteration in expression.</p></div><div><h3>Results</h3><p>The six multi-omics-based identified genes, RUNX1, MSC, ADA, TREML1, TGFA, and VWF, showed higher expression with enrichment of active histone marks and hypomethylated CpG in ccRCC. In continuation, the identified genes were validated by an independent dataset and showed a correlation with nodal and metastatic status. Furthermore, gene ontology and pathway analysis revealed that immune-related pathways are activated in ccRCC patients.</p></div><div><h3>Conclusions</h3><p>The network analysis of six overexpressed genes suggests their potential role in an immunosuppressive environment, leading to tumor progression and poor prognosis. Our study shows that the multi-omics approach helps unravel complex biology for patient subtyping and proposes combination strategies with epi-drugs for more precise immunotherapy in ccRCC.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncoupling of Cytochrome P450 2B6 and stimulation of reactive oxygen species production in pharmacogenomic alleles affected by interethnic variability","authors":"Sabrina Yamoune ,&nbsp;Julian Peter Müller ,&nbsp;Immaculate Mbongo Langmia ,&nbsp;Catharina Scholl ,&nbsp;Julia Carolin Stingl","doi":"10.1016/j.bbagen.2024.130595","DOIUrl":"10.1016/j.bbagen.2024.130595","url":null,"abstract":"<div><p>Cytochrome P450 mediated substrate metabolism is generally characterized by the formation of reactive intermediates. <em>In vitro</em> and <em>in vivo</em> reaction uncoupling, results in the accumulation and dissociation of reactive intermediates, leading to increased ROS formation. The susceptibility towards uncoupling and altered metabolic activity is partly modulated by pharmacogenomic alleles resulting in amino acid substitutions. A large variability in the prevalence of these alleles has been demonstrated in CYP2B6, with some being predominantly unique to African populations.</p><p>The aim of this study is to characterize the uncoupling potential of recombinant CYP2B6*1, CYP2B6*6 and CYP2B6*34 metabolism of specific substrates.</p><p>Therefore, functional effects of these alterations on enzyme activity were determined by quantification of bupropion, efavirenz and ketamine biotransformation using HPLC-MS/MS. Determination of H₂O₂ levels was performed by the AmplexRed/horseradish peroxidase assay.</p><p>Our studies of the amino acid substitutions Q172H, K262R and R487S revealed an exclusive use of the peroxide shunt for the metabolism of bupropion and ketamine by CYP2B6*K262R. Ketamine was also identified as a trigger for the peroxide shunt in CYP2B6*1 and all variants. Concurrently, ketamine acted as an uncoupler for all enzymes. We further showed that the expressed CYP2B6*34 allele results in the highest H₂O₂ formation.</p><p>We therefore conclude that the reaction uncoupling and peroxide shunt are directly linked and can be substrate specifically induced with K262R carriers being most likely to use the peroxide shunt and R487S carrier being most prone to reaction uncoupling. This elucidates the functional diversity of pharmacogenomics in drug metabolism and safety.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0304416524000382/pdfft?md5=96675258f2f827b2df4a2f5f4da194ef&pid=1-s2.0-S0304416524000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and biochemical characterization of active sites mutant in human inorganic pyrophosphatase","authors":"Shuping Zheng ,&nbsp;Chenhua Zheng ,&nbsp;Sishi Chen ,&nbsp;Jianpeng Guo ,&nbsp;Lirui Huang ,&nbsp;Zhenhong Huang ,&nbsp;Sunting Xu ,&nbsp;Yihan Wu ,&nbsp;Shunfa Li ,&nbsp;Junjin Lin ,&nbsp;Yiqing You ,&nbsp;Fen Hu","doi":"10.1016/j.bbagen.2024.130594","DOIUrl":"10.1016/j.bbagen.2024.130594","url":null,"abstract":"<div><p>Inorganic pyrophosphatases (PPases) are enzymes that catalyze the conversion of inorganic pyrophosphate (PPi) into phosphate (Pi). Human inorganic pyrophosphatase 1 (Hu-PPase) exhibits high expression levels in a variety of tumors and plays roles in cell proliferation, apoptosis, invasion and metastasis, making it a promising prognostic biomarker and a target for cancer therapy. Despite its widespread presence, the catalytic mechanism of Hu-PPase in humans remains inadequately understood. The signature motif amino acid sequence (DXDPXD) within the active sites of PPases is preserved across different species. In this research, an enzymatic activity assay revealed that mutations led to a notable reduction in enzymatic function, although the impact of the four amino acids on the activity of the pocket varied. To investigate the influence of these residues on the substrate binding and enzymatic function of PPase, the crystal structure of the Hu-PPase-ED quadruple mutant (D116A/D118A/P119A/D121A) was determined at 1.69 Å resolution. The resulting structure maintained a barrel-like shape similar to that of the wild-type, albeit lacking Mg²⁺ ions. Molecular docking analysis demonstrated a decreased ability of Hu-PPase-ED to bind to PPi. Further, molecular dynamics simulation analysis indicated that the mutation rendered the loop of Mg²⁺ ion-binding residues less stable. Therefore, the effect on enzyme activity did not result from a change in the gross protein structure but rather from a mutation that abolished the Mg²⁺-coordinating groups, thereby eliminating Mg²⁺ binding and leading to the loss of enzyme activity.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into flowering mechanisms in apple (Malus × domestica Borkh.) amidst climate change: An exploration of genetic and epigenetic factors","authors":"Anshul Kumar ,&nbsp;Muntazir Mushtaq ,&nbsp;Pankaj Kumar ,&nbsp;Dharam Paul Sharma ,&nbsp;Vijay Gahlaut","doi":"10.1016/j.bbagen.2024.130593","DOIUrl":"10.1016/j.bbagen.2024.130593","url":null,"abstract":"<div><p>Apple (<em>Malus × domestica</em> Borkh.) holds a prominent position among global temperate fruit crops, with flowering playing a crucial role in both production and breeding. This review delves into the intricate mechanisms governing apple flowering amidst the backdrop of climate change, acknowledging the profound influence of external and internal factors on biennial bearing, flower bud quality, and ultimately, fruit quality. Notably, the challenge faced in major apple production regions is not an inadequacy of flowers but an excess, leading to compromised fruit quality necessitating thinning practices. Climate change exacerbates these challenges, rendering apple trees more susceptible to crop failure due to unusual weather events, such as reduced winter snowfall, early spring cold weather, and hailstorms during flowering and fruit setting. Altered climatic conditions, exemplified by increased spring warming coupled with sub-freezing temperatures, negatively impact developing flower buds and decrease overall crop production. Furthermore, changing winter conditions affect chilling accumulation, disrupting flower development and synchronicity. Although the physiological perception of apple flowering has been reviewed in the past, the genetic, epigenetic, and multi-omics regulatory mechanisms governing floral induction and flowering are still rarely discussed in the case of apple flowering. This article comprehensively reviews the latest literature encompassing all aspects of apple flowering, aiming to broaden our understanding and address flowering challenges while also laying a solid foundation for future research in developing cultivars that are ideally adapted to climate change.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-fetoprotein upregulates hepatocellular carcinoma cell-intrinsic PD-1 expression through the LATS2/YAP/TEAD1 pathway","authors":"Guangxian Leng ,&nbsp;Hongxia Gong ,&nbsp;Guiyuan Liu ,&nbsp;Yin Kong ,&nbsp;Liuqing Guo ,&nbsp;Youcheng Zhang","doi":"10.1016/j.bbagen.2024.130592","DOIUrl":"10.1016/j.bbagen.2024.130592","url":null,"abstract":"<div><h3>Background</h3><p>Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression.</p></div><div><h3>Methods</h3><p>The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1.</p></div><div><h3>Results</h3><p>The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter.</p></div><div><h3>Conclusion</h3><p>AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis.</p></div><div><h3>General</h3><p>Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.</p></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}