Life Science Alliance最新文献_第5页

ETV2 induces endothelial, but not hematopoietic, lineage specification in birds. ETV2 可诱导鸟类内皮细胞而非造血细胞系的形成。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-03 DOI: 10.26508/lsa.202402694

Wei Weng, Yuan Deng, Ruslan Deviatiiarov, Sofiane Hamidi, Eriko Kajikawa, Oleg Gusev, Hiroshi Kiyonari, Guojie Zhang, Guojun Sheng

{"title":"ETV2 induces endothelial, but not hematopoietic, lineage specification in birds.","authors":"Wei Weng, Yuan Deng, Ruslan Deviatiiarov, Sofiane Hamidi, Eriko Kajikawa, Oleg Gusev, Hiroshi Kiyonari, Guojie Zhang, Guojun Sheng","doi":"10.26508/lsa.202402694","DOIUrl":"https://doi.org/10.26508/lsa.202402694","url":null,"abstract":"Cardiovascular system develops from the lateral plate mesoderm. Its three primary cell lineages (hematopoietic, endothelial, and muscular) are specified by the sequential actions of conserved transcriptional factors. ETV2, a master regulator of mammalian hemangioblast development, however, is absent in the chicken genome and acts downstream of NPAS4L in zebrafish. Here, we investigated the epistatic relationship between NPAS4L and ETV2 in avian hemangioblast development. We showed that ETV2 is deleted in all 363 avian genomes analyzed. Mouse ETV2 induced LMO2, but not NPAS4L or SCL, expression in chicken mesoderm. Squamate (lizards, geckos, and snakes) genomes contain both NPAS4L and ETV2 In Madagascar ground gecko, both genes were expressed in developing hemangioblasts. Gecko ETV2 induced only LMO2 in chicken mesoderm. We propose that both NPAS4L and ETV2 were present in ancestral amniote, with ETV2 acting downstream of NPAS4L in endothelial lineage specification. ETV2 may have acted as a pioneer factor by promoting chromatin accessibility of endothelial-specific genes and, in parallel with NPAS4L loss in ancestral mammals, has gained similar function in regulating blood-specific genes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina. 人类 CRB1 和 CRB2 在视网膜中形成同源和异源蛋白复合物。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-03 DOI: 10.26508/lsa.202302440

Isabel F Stehle, Joel A Imventarza, Franziska Woerz, Felix Hoffmann, Karsten Boldt, Tina Beyer, Peter Mj Quinn, Marius Ueffing

{"title":"Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina.","authors":"Isabel F Stehle, Joel A Imventarza, Franziska Woerz, Felix Hoffmann, Karsten Boldt, Tina Beyer, Peter Mj Quinn, Marius Ueffing","doi":"10.26508/lsa.202302440","DOIUrl":"https://doi.org/10.26508/lsa.202302440","url":null,"abstract":"Crumbs homolog 1 (CRB1) is one of the key genes linked to retinitis pigmentosa and Leber congenital amaurosis, which are characterized by a high clinical heterogeneity. The Crumbs family member CRB2 has a similar protein structure to CRB1, and in zebrafish, Crb2 has been shown to interact through the extracellular domain. Here, we show that CRB1 and CRB2 co-localize in the human retina and human iPSC-derived retinal organoids. In retina-specific pull-downs, CRB1 was enriched in CRB2 samples, supporting a CRB1-CRB2 interaction. Furthermore, novel interactors of the crumbs complex were identified, representing a retina-derived protein interaction network. Using co-immunoprecipitation, we further demonstrate that human canonical CRB1 interacts with CRB1 and CRB2, but not with CRB3, which lacks an extracellular domain. Next, we explored how missense mutations in the extracellular domain affect CRB1-CRB2 interactions. We observed no or a mild loss of CRB1-CRB2 interaction, when interrogating various CRB1 or CRB2 missense mutants in vitro. Taken together, our results show a stable interaction of human canonical CRB2 and CRB1 in the retina.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive meta-analysis reveals distinct gene expression signatures of MASLD progression 综合荟萃分析揭示了 MASLD 进展的不同基因表达特征

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-02 DOI: 10.26508/lsa.202302517

Ignazio S. Piras, J. DiStefano

引用次数: 0

Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life. 对哺乳动物生命至关重要的核 HAPSTR1-HUWE1 通路的严格调控。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-03-07 Print Date: 2024-05-01 DOI: 10.26508/lsa.202302370

David R Amici, Sammy Alhayek, Austin T Klein, Yi-Zhi Wang, Anika P Wilen, Weimin Song, Pei Zhu, Abhishek Thakkar, McKenzi A King, Adam Wt Steffeck, Milad J Alasady, Clara Peek, Jeffrey N Savas, Marc L Mendillo

{"title":"Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.","authors":"David R Amici, Sammy Alhayek, Austin T Klein, Yi-Zhi Wang, Anika P Wilen, Weimin Song, Pei Zhu, Abhishek Thakkar, McKenzi A King, Adam Wt Steffeck, Milad J Alasady, Clara Peek, Jeffrey N Savas, Marc L Mendillo","doi":"10.26508/lsa.202302370","DOIUrl":"10.26508/lsa.202302370","url":null,"abstract":"The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, although HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex. KRAS 的致癌突变通过 CUL3/LZTR1 E3 连接酶复合物调节其周转。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-03-07 Print Date: 2024-05-01 DOI: 10.26508/lsa.202302245

Andreas Damianou, Zhu Liang, Frederik Lassen, Iolanda Vendrell, George Vere, Svenja Hester, Philip D Charles, Adan Pinto-Fernandez, Alberto Santos, Roman Fischer, Benedikt M Kessler

{"title":"Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex.","authors":"Andreas Damianou, Zhu Liang, Frederik Lassen, Iolanda Vendrell, George Vere, Svenja Hester, Philip D Charles, Adan Pinto-Fernandez, Alberto Santos, Roman Fischer, Benedikt M Kessler","doi":"10.26508/lsa.202302245","DOIUrl":"10.26508/lsa.202302245","url":null,"abstract":"KRAS is a proto-oncogene encoding a small GTPase. Mutations contribute to ∼30% of human solid tumours, including lung adenocarcinoma, pancreatic, and colorectal carcinomas. Most KRAS activating mutations interfere with GTP hydrolysis, essential for its role as a molecular switch, leading to alterations in their molecular environment and oncogenic signalling. However, the precise signalling cascades these mutations affect are poorly understood. Here, APEX2 proximity labelling was used to profile the molecular environment of WT, G12D, G13D, and Q61H-activating KRAS mutants under starvation and stimulation conditions. Through quantitative proteomics, we demonstrate the presence of known KRAS interactors, including ARAF and LZTR1, which are differentially captured by WT and KRAS mutants. Notably, the KRAS mutations G12D, G13D, and Q61H abrogate their association with LZTR1, thereby affecting turnover. Elucidating the implications of LZTR1-mediated regulation of KRAS protein levels in cancer may offer insights into therapeutic strategies targeting KRAS-driven malignancies.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Systemic metabolic depletion of gut microbiome undermines responsiveness to melanoma immunotherapy. 肠道微生物群的全身代谢消耗会削弱对黑色素瘤免疫疗法的反应能力。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-03-06 Print Date: 2024-05-01 DOI: 10.26508/lsa.202302480

Natalia V Zakharevich, Maxim D Morozov, Vera A Kanaeva, Mikhail S Filippov, Tatyana I Zyubko, Artem B Ivanov, Vladimir I Ulyantsev, Ksenia M Klimina, Evgenii I Olekhnovich

{"title":"Systemic metabolic depletion of gut microbiome undermines responsiveness to melanoma immunotherapy.","authors":"Natalia V Zakharevich, Maxim D Morozov, Vera A Kanaeva, Mikhail S Filippov, Tatyana I Zyubko, Artem B Ivanov, Vladimir I Ulyantsev, Ksenia M Klimina, Evgenii I Olekhnovich","doi":"10.26508/lsa.202302480","DOIUrl":"10.26508/lsa.202302480","url":null,"abstract":"Immunotherapy has proven to be a boon for patients battling metastatic melanoma, significantly improving their clinical condition and overall quality of life. A compelling link between the composition of the gut microbiome and the efficacy of immunotherapy has been established in both animal models and human patients. However, the precise biological mechanisms by which gut microbes influence treatment outcomes remain poorly understood. Using a robust dataset of 680 fecal metagenomes from melanoma patients, a detailed catalog of metagenome-assembled genomes (MAGs) was constructed to explore the compositional and functional properties of the gut microbiome. Our study uncovered significant findings that deepen the understanding of the intricate relationship between gut microbes and the efficacy of melanoma immunotherapy. In particular, we discovered the specific metagenomic profile of patients with favorable treatment outcomes, characterized by a prevalence of MAGs with increased overall metabolic potential and proficiency in polysaccharide utilization, along with those responsible for cobalamin and amino acid production. Furthermore, our investigation of the biosynthetic pathways of short-chain fatty acids, known for their immunomodulatory role, revealed a differential abundance of these pathways among the specific MAGs. Among others, the cobalamin-dependent Wood-Ljungdahl pathway of acetate synthesis was directly associated with responsiveness to melanoma immunotherapy.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Altered myocardial lipid regulation in junctophilin-2-associated familial cardiomyopathies. 结ophilin-2相关家族性心肌病的心肌脂质调节改变

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-03-04 Print Date: 2024-05-01 DOI: 10.26508/lsa.202302330

Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens

{"title":"Altered myocardial lipid regulation in junctophilin-2-associated familial cardiomyopathies.","authors":"Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens","doi":"10.26508/lsa.202302330","DOIUrl":"10.26508/lsa.202302330","url":null,"abstract":"Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and DCM, suggesting a common metabolic alteration in both models. On the contrary, significantly increased di- and triglycerides, and decreased co-enzyme were only found in mice with HCM. Moreover, mice with DCM uniquely exhibited elevated levels of cholesterol ester. Further in-depth analysis revealed significantly altered metabolites from all the lipid classes with either similar or opposing trends in JPH2 mutant mice with HCM or DCM. Together, these studies revealed, for the first time, unique alterations in the cardiac lipid composition-including distinct increases in neutral lipids and decreases in polar membrane lipids-in mice with HCM and DCM were caused by distinct JPH2 variants. These studies may aid the development of novel biomarkers or therapeutics for these inherited disorders.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Ageing-dependent thiol oxidation reveals early oxidation of proteins with core proteostasis functions. 衰老依赖性硫醇氧化揭示了具有核心蛋白稳态功能的蛋白质的早期氧化。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-02-21 DOI: 10.26508/lsa.202302300

Katarzyna Jonak, Ida Suppanz, Julian Bender, Agnieszka Chacinska, Bettina Warscheid, Ulrike Topf

{"title":"Ageing-dependent thiol oxidation reveals early oxidation of proteins with core proteostasis functions.","authors":"Katarzyna Jonak, Ida Suppanz, Julian Bender, Agnieszka Chacinska, Bettina Warscheid, Ulrike Topf","doi":"10.26508/lsa.202302300","DOIUrl":"https://doi.org/10.26508/lsa.202302300","url":null,"abstract":"Oxidative post-translational modifications of protein thiols are well recognized as a readily occurring alteration of proteins, which can modify their function and thus control cellular processes. The development of techniques enabling the site-specific assessment of protein thiol oxidation on a proteome-wide scale significantly expanded the number of known oxidation-sensitive protein thiols. However, lacking behind are large-scale data on the redox state of proteins during ageing, a physiological process accompanied by increased levels of endogenous oxidants. Here, we present the landscape of protein thiol oxidation in chronologically aged wild-type Saccharomyces cerevisiae in a time-dependent manner. Our data determine early-oxidation targets in key biological processes governing the de novo production of proteins, protein folding, and degradation, and indicate a hierarchy of cellular responses affected by a reversible redox modification. Comparison with existing datasets in yeast, nematode, fruit fly, and mouse reveals the evolutionary conservation of these oxidation targets. To facilitate accessibility, we integrated the cross-species comparison into the newly developed OxiAge Database.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139926218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breast implant surface topography triggers a chronic-like inflammatory response. 乳房植入物表面形貌会引发慢性炎症反应。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-02-21 DOI: 10.26508/lsa.202302132

Valeriano Vinci, Cristina Belgiovine, Gerardus Janszen, Benedetta Agnelli, Luca Pellegrino, Francesca Calcaterra, Assunta Cancellara, Roberta Ciceri, Alessandra Benedetti, Cindy Cardenas, Federico Colombo, Domenico Supino, Alessia Lozito, Edoardo Caimi, Marta Monari, Francesco Maria Klinger, Giovanna Riccipetitoni, Alessandro Raffaele, Patrizia Comoli, Paola Allavena, Domenico Mavilio, Luca Di Landro, Marco Klinger, Roberto Rusconi

{"title":"Breast implant surface topography triggers a chronic-like inflammatory response.","authors":"Valeriano Vinci, Cristina Belgiovine, Gerardus Janszen, Benedetta Agnelli, Luca Pellegrino, Francesca Calcaterra, Assunta Cancellara, Roberta Ciceri, Alessandra Benedetti, Cindy Cardenas, Federico Colombo, Domenico Supino, Alessia Lozito, Edoardo Caimi, Marta Monari, Francesco Maria Klinger, Giovanna Riccipetitoni, Alessandro Raffaele, Patrizia Comoli, Paola Allavena, Domenico Mavilio, Luca Di Landro, Marco Klinger, Roberto Rusconi","doi":"10.26508/lsa.202302132","DOIUrl":"https://doi.org/10.26508/lsa.202302132","url":null,"abstract":"Breast implants are extensively employed for both reconstructive and esthetic purposes. However, the safety of breast implants with textured surfaces has been questioned, owing to a potential correlation with anaplastic large-cell lymphoma and the recurrence of breast cancer. This study investigates the immune response elicited by different prosthetic surfaces, focusing on the comparison between macrotextured and microtextured breast implants. Through the analysis of intraoperatively harvested periprosthetic fluids and cell culture experiments on surface replicas, we demonstrate that macrotextured surfaces elicit a more pronounced chronic-like activation of leucocytes and an increased release of inflammatory cytokines, in contrast to microtextured surfaces. In addition, in vitro fluorescent imaging of leucocytes revealed an accumulation of lymphocytes within the cavities of the macrotextured surfaces, indicating that the physical entrapment of these cells may contribute to their activation. These findings suggest that the topography of implant surfaces plays a significant role in promoting a chronic-like inflammatory environment, which could be a contributing factor in the development of lymphomas associated with a wide range of implantable devices.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139926212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variety in the USP deubiquitinase catalytic mechanism. USP 去泛素酶催化机制的多样性。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-14 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302533

Niels Keijzer, Anu Priyanka, Yvette Stijf-Bultsma, Alexander Fish, Malte Gersch, Titia K Sixma

{"title":"Variety in the USP deubiquitinase catalytic mechanism.","authors":"Niels Keijzer, Anu Priyanka, Yvette Stijf-Bultsma, Alexander Fish, Malte Gersch, Titia K Sixma","doi":"10.26508/lsa.202302533","DOIUrl":"10.26508/lsa.202302533","url":null,"abstract":"The ubiquitin-specific protease (USP) family of deubiquitinases (DUBs) controls cellular ubiquitin-dependent signaling events. This generates therapeutic potential, with active-site inhibitors in preclinical and clinical studies. Understanding of the USP active site is primarily guided by USP7 data, where the catalytic triad consists of cysteine, histidine, and a third residue (third critical residue), which polarizes the histidine through a hydrogen bond. A conserved aspartate (fourth critical residue) is directly adjacent to this third critical residue. Although both critical residues accommodate catalysis in USP2, these residues have not been comprehensively investigated in other USPs. Here, we quantitatively investigate their roles in five USPs. Although USP7 relies on the third critical residue for catalysis, this residue is dispensable in USP1, USP15, USP40, and USP48, where the fourth critical residue is vital instead. Furthermore, these residues vary in importance for nucleophilic attack. The diverging catalytic mechanisms of USP1 and USP7 are independent of substrate and retained in cells for USP1. This unexpected variety of catalytic mechanisms in this well-conserved protein family may generate opportunities for selective targeting of individual USPs.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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