Bioscience Reports最新文献

{"title":"Structural characterization of DNA-binding domain of essential mammalian protein TTF 1.","authors":"Gajender Singh, Abhinetra Jagdish Bhopale, Saloni Khatri, Prashant Prakash, Rajnish Kumar, Sukh Mahendra Singh, Samarendra Kumar Singh","doi":"10.1042/BSR20240800","DOIUrl":"10.1042/BSR20240800","url":null,"abstract":"<p><p>Transcription Termination Factor 1 (TTF1) is a multifunctional mammalian protein with vital roles in various cellular processes, including Pol I-mediated transcription initiation and termination, pre-rRNA processing, chromatin remodelling, DNA damage repair, and polar replication fork arrest. It comprises two distinct functional regions; the N-terminal regulatory region (1-445 aa), and the C-terminal catalytic region (445-859 aa). The Myb domain located at the C-terminal region is a conserved DNA binding domain spanning from 550 to 732 aa (183 residues). Despite its critical role in various cellular processes, the physical structure of TTF1 remains unsolved. Attempts to purify the functional TTF1 protein have been unsuccessful till date. Therefore, we focused on characterizing the Myb domain of this essential protein. We started with predicting a 3-D model of the Myb domain using homology modelling, and ab-initio method. We then determined its stability through MD simulation in an explicit solvent. The model predicted is highly stable, which stabilizes at 200ns. To experimentally validate the computational model, we cloned and expressed the codon optimized Myb domain into a bacterial expression vector and purified the protein to homogeneity. Further, characterization of the protein shows that, Myb domain is predominantly helical (65%) and is alone sufficient to bind the Sal Box DNA. This is the first-ever study to report a complete in silico model of the Myb domain, which is physically characterized. The above study will pave the way towards solving the atomic structure of this essential mammalian protein.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900877","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":"Transglutaminase 2-mediated histone monoaminylation and its role in cancer.","authors":"Huapeng Li, Jinghua Wu, Nan Zhang, Qingfei Zheng","doi":"10.1042/BSR20240493","DOIUrl":"10.1042/BSR20240493","url":null,"abstract":"<p><p>Transglutaminase 2 (TGM2) has been known as a well-characterized factor regulating the progression of multiple types of cancer, due to its multifunctional activities and the ubiquitous signaling pathways it is involved in. As a member of the transglutaminase family, TGM2 catalyzes protein post-translational modifications (PTMs), including monoaminylation, amide hydrolysis, cross-linking, etc., through the transamidation of variant glutamine-containing protein substrates. Recent discoveries revealed histone as an important category of TGM2 substrates, thus identifying histone monoaminylation as an emerging epigenetic mark, which is highly enriched in cancer cells and possesses significant regulatory functions of gene transcription. In this review, we will summarize recent advances in TGM2-mediated histone monoaminylation as well as its role in cancer and discuss the key research methodologies to better understand this unique epigenetic mark, thereby shedding light on the therapeutic potential of TGM2 as a druggable target in cancer treatment.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900878","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":"Tamoxifen metabolites treatment promotes ERα+ transition to triple negative phenotype in vitro, effects of LDL in chemoresistance.","authors":"Andrea Muñoz-Ayala, Brenda Chimal-Vega, Nicolás Serafín-Higuera, Octavio Galindo-Hernández, Gladys Ramírez-Rosales, Iván Córdova-Guerrero, Luis Fernando Gómez-Lucas, Victor García-González","doi":"10.1042/BSR20240444","DOIUrl":"10.1042/BSR20240444","url":null,"abstract":"<p><strong>Objective: </strong>Estrogen receptor-positive (ER+) breast cancer represents about 80% of cases, tamoxifen is the election neoadjuvant chemotherapy. However, a large percentage of patients develop chemoresistance, compromising recovery. Clinical evidence suggests that high plasmatic levels of low-density lipoproteins (LDL) could promote cancer progression. The present study analyzed the effect of LDL on the primary plasmatic active Tamoxifen's metabolites resistance acquisition, 4-hydroxytamoxifen (4OH-Tam) and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), in breast cancer ERα + cells (MCF-7).</p><p><strong>Methods: </strong>Two resistant cellular variants, MCF-7Var-H and MCF-7Var-I, were generated by a novel strategy and their phenotype features were evaluated. Phenotypic assessment was performed by MTT assays, cytometry, immunofluorescence microscopy, zymography and protein expression analysis.</p><p><strong>Results: </strong>MCF-7Var-H, generated only with tamoxifen metabolites, showed a critical down-regulation in hormone receptors, augmented migration capacity, metalloprotease 9 extracellular medium excretion, and a mesenchymal morphology in contrast with native MCF-7, suggesting the transition towards Triple-negative breast cancer (TNBC) phenotype. In contrast, MCF-7Var-I which was generated in a high LDL media, showed only a slight upregulation in ER and other less noticeable metabolic adaptations. Results suggest a potential role of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in phenotypic differences observed among variants.</p><p><strong>Conclusion: </strong>LDL high or low concentrations during Tamoxifen´s metabolites chemoresistance acquisition leads to different cellular mechanisms related to chemoresistance. A novel adaptative cellular response associated with Nrf2 activity could be implicated.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733495","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":"Retraction: Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MPAK pathway.","authors":"","doi":"10.1042/BSR-2018-1451_RET","DOIUrl":"10.1042/BSR-2018-1451_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"44 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016256","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":"Retraction: High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress.","authors":"","doi":"10.1042/BSR-2020-0262_RET","DOIUrl":"10.1042/BSR-2020-0262_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"44 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016260","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":"Retraction: Bone morphogenetic protein-7 retards cell subculture-induced senescence of human nucleus pulposus cells through activating the PI3K/Akt pathway.","authors":"","doi":"10.1042/BSR-2018-2312_RET","DOIUrl":"10.1042/BSR-2018-2312_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"44 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016257","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":"Retraction: Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment.","authors":"","doi":"10.1042/BSR-2018-1530_RET","DOIUrl":"10.1042/BSR-2018-1530_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"44 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016269","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":"Retraction: Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro.","authors":"","doi":"10.1042/BSR-2019-0126_RET","DOIUrl":"10.1042/BSR-2019-0126_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"44 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016272","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":"Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.","authors":"K Ravi Acharya, Kyle S Gregory, Edward D Sturrock","doi":"10.1042/BSR20240130","DOIUrl":"10.1042/BSR20240130","url":null,"abstract":"<p><p>Human somatic angiotensin-converting enzyme (ACE) is a key zinc metallopeptidase that plays a pivotal role in the renin-angiotensin-aldosterone system (RAAS) by regulating blood pressure and electrolyte balance. Inhibition of ACE is a cornerstone in the management of hypertension, cardiovascular diseases, and renal disorders. Recent advances in structural biology techniques have provided invaluable insights into the molecular mechanisms underlying ACE inhibition, facilitating the design and development of more effective therapeutic agents. This review focuses on the latest advancements in elucidating the structural basis for ACE inhibition. High-resolution crystallographic studies of minimally glycosylated individual domains of ACE have revealed intricate molecular details of the ACE catalytic N- and C-domains, and their detailed interactions with clinically relevant and newly designed domain-specific inhibitors. In addition, the recently elucidated structure of the glycosylated form of full-length ACE by cryo-electron microscopy (cryo-EM) has shed light on the mechanism of ACE dimerization and revealed continuous conformational changes which occur prior to ligand binding. In addition to these experimental techniques, computational approaches have also played a pivotal role in elucidating the structural basis for ACE inhibition. Molecular dynamics simulations and computational docking studies have provided atomic details of inhibitor binding kinetics and energetics, facilitating the rational design of novel ACE inhibitors with improved potency and selectivity. Furthermore, computational analysis of the motions observed by cryo-EM allowed the identification of allosteric binding sites on ACE. This affords new opportunities for the development of next-generation allosteric inhibitors with enhanced pharmacological properties. Overall, the insights highlighted in this review could enable the rational design of novel ACE inhibitors with improved efficacy and safety profiles, ultimately leading to better therapeutic outcomes for patients with hypertension and cardiovascular diseases.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750995","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":"Adipose tissue-liver cross-talk: a route to hepatic dysfunction in pregnant women with obesity.","authors":"Diana Sousa, Carina C Magalhães, Paulo Matafome, Susana P Pereira","doi":"10.1042/BSR20231679","DOIUrl":"10.1042/BSR20231679","url":null,"abstract":"<p><p>Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854643","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}