Advances in biological regulation最新文献_第8页

Splicing factor mutations in the myelodysplastic syndromes: Role of key aberrantly spliced genes in disease pathophysiology and treatment 剪接因子突变在骨髓增生异常综合征:关键异常剪接基因在疾病病理生理和治疗中的作用

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100920

Andrea Pellagatti, Jacqueline Boultwood

{"title":"Splicing factor mutations in the myelodysplastic syndromes: Role of key aberrantly spliced genes in disease pathophysiology and treatment","authors":"Andrea Pellagatti, Jacqueline Boultwood","doi":"10.1016/j.jbior.2022.100920","DOIUrl":"10.1016/j.jbior.2022.100920","url":null,"abstract":"<div><p>Mutations of splicing factor genes (including <em>SF3B1</em>, <em>SRSF2</em>, <em>U2AF1</em> and <em>ZRSR2</em>) occur in more than half of all patients with myelodysplastic syndromes (MDS), a heterogeneous group of myeloid neoplasms. Splicing factor mutations lead to aberrant pre-mRNA splicing of many genes, some of which have been shown in functional studies to impact on hematopoiesis and to contribute to the MDS phenotype. This clearly demonstrates that impaired spliceosome function plays an important role in MDS pathophysiology. Recent studies that harnessed the power of induced pluripotent stem cell (iPSC) and CRISPR/Cas9 gene editing technologies to generate new iPSC-based models of splicing factor mutant MDS, have further illuminated the role of key downstream target genes. The aberrantly spliced genes and the dysregulated pathways associated with splicing factor mutations in MDS represent potential new therapeutic targets. Emerging data has shown that <em>IRAK4</em> is aberrantly spliced in <em>SF3B1</em> and <em>U2AF1</em> mutant MDS, leading to hyperactivation of NF-κB signaling. Pharmacological inhibition of IRAK4 has shown efficacy in pre-clinical studies and in MDS clinical trials, with higher response rates in patients with splicing factor mutations. Our increasing knowledge of the effects of splicing factor mutations in MDS is leading to the development of new treatments that may benefit patients harboring these mutations.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100920"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10583466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase 肽基脯氨酸异构酶Pin1对真核蛋白激酶的调控

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100938

Xiao-Ru Chen, Tatyana I. Igumenova

{"title":"Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase","authors":"Xiao-Ru Chen, Tatyana I. Igumenova","doi":"10.1016/j.jbior.2022.100938","DOIUrl":"10.1016/j.jbior.2022.100938","url":null,"abstract":"<div><p>The peptidyl-prolyl isomerase Pin1 cooperates with proline-directed kinases and phosphatases to regulate multiple oncogenic pathways. Pin1 specifically recognizes phosphorylated Ser/Thr-Pro motifs in proteins and catalyzes their <em>cis</em>-<em>trans</em> isomerization. The Pin1-catalyzed conformational changes determine the stability, activity, and subcellular localization of numerous protein substrates. We conducted a survey of eukaryotic protein kinases that are regulated by Pin1 and whose Pin1 binding sites have been identified. Our analyses reveal that Pin1 target sites in kinases do not fall exclusively within the intrinsically disordered regions of these enzymes. Rather, they fall into three groups based on their location: (i) within the catalytic kinase domain, (ii) in the C-terminal kinase region, and (iii) in regulatory domains. Some of the kinases downregulated by Pin1 activity are tumor-suppressing, and all kinases upregulated by Pin1 activity are functionally pro-oncogenic. These findings further reinforce the rationale for developing Pin1-specific inhibitors as attractive pharmaceuticals for cancer therapy.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100938"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174115","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}

引用次数: 1

IL-7 and IL-7R in health and disease: An update through COVID times IL-7和IL-7R在健康和疾病中的作用:通过COVID时代的更新

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100940

Marta B. Fernandes, João T. Barata

引用次数: 24

Modified lipidomic profile of cancer-associated small extracellular vesicles facilitates tumorigenic behaviours and contributes to disease progression 癌症相关的细胞外小泡的脂质组学特征的改变促进了致瘤行为并有助于疾病进展

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100935

Jordan Fyfe, Pratibha Malhotra, Marco Falasca

引用次数: 1

PIP kinases: A versatile family that demands further therapeutic attention PIP激酶:一个多功能家族，需要进一步的治疗关注

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100939

Alicia Llorente, Gurpreet K. Arora , Shea F. Grenier , Brooke M. Emerling

引用次数: 1

From form to function: m6A methylation links mRNA structure to metabolism 从形式到功能：m6A甲基化将mRNA结构与代谢联系起来

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100926

Braulio Martinez De La Cruz, Marousa Darsinou, Antonella Riccio

引用次数: 1

Advances in MDS/AML and inositide signalling MDS/AML和肌苷信号传导的研究进展

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2023.100955

Alessia De Stefano , Maria Vittoria Marvi , Antonietta Fazio , James A. McCubrey , Pann-Ghill Suh , Stefano Ratti , Giulia Ramazzotti , Lucia Manzoli , Lucio Cocco , Matilde Y. Follo

引用次数: 1

Phospholipase D and cancer metastasis: A focus on exosomes 磷脂酶D与肿瘤转移:以外泌体为中心

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100924

Alexander Wolf, Emeline Tanguy, Qili Wang, Stéphane Gasman, Nicolas Vitale

{"title":"Phospholipase D and cancer metastasis: A focus on exosomes","authors":"Alexander Wolf, Emeline Tanguy, Qili Wang, Stéphane Gasman, Nicolas Vitale","doi":"10.1016/j.jbior.2022.100924","DOIUrl":"10.1016/j.jbior.2022.100924","url":null,"abstract":"<div><p>In mammals, phospholipase D (PLD) enzymes involve 6 isoforms, of which only three have established lipase activity to produce the signaling lipid phosphatidic acid (PA). This phospholipase activity has been postulated to contribute to cancer progression for over three decades now, but the exact mechanisms involved have yet to be uncovered. Indeed, using various models, an altered PLD activity has been proposed altogether to increase cell survival rate, promote angiogenesis, boost rapamycin resistance, and favor metastasis. Although for some part, the molecular pathways by which this increase in PA is pro-oncogenic are partially known, the pleiotropic functions of PA make it quite difficult to distinguish which among these simple signaling pathways is responsible for each of these PLD facets. In this review, we will describe an additional potential contribution of PA generated by PLD1 and PLD2 in the biogenesis, secretion, and uptake of exosomes. Those extracellular vesicles are now viewed as membrane vehicles that carry informative molecules able to modify the fate of receiving cells at distance from the original tumor to favor homing of metastasis. The perspectives for a better understanding of these complex role of PLDs will be discussed.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100924"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9173474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Key to photograph of participants 参加者照片的钥匙

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100952

引用次数: 0

AP-4 loss in CRISPR-edited zebrafish affects early embryo development crispr编辑的斑马鱼AP-4缺失影响早期胚胎发育

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100945

Olivia G. Pembridge , Natalie S. Wallace , Thomas P. Clements , Lauren P. Jackson

{"title":"AP-4 loss in CRISPR-edited zebrafish affects early embryo development","authors":"Olivia G. Pembridge , Natalie S. Wallace , Thomas P. Clements , Lauren P. Jackson","doi":"10.1016/j.jbior.2022.100945","DOIUrl":"10.1016/j.jbior.2022.100945","url":null,"abstract":"<div><p>Mutations in the heterotetrametric adaptor protein 4 (AP-4; ε/β4/μ4/σ4 subunits) membrane trafficking coat complex lead to complex neurological disorders characterized by spastic paraplegia, microcephaly, and intellectual disabilities. Understanding molecular mechanisms underlying these disorders continues to emerge with recent identification of an essential autophagy protein, ATG9A, as an AP-4 cargo. Significant progress has been made uncovering AP-4 function in cell culture and patient-derived cell lines, and ATG9A trafficking by AP-4 is considered a potential target for gene therapy approaches. In contrast, understanding how AP-4 trafficking affects development and function at the organismal level has long been hindered by loss of conserved AP-4 genes in key model systems (<em>S. cerevisiae</em>, <em>C. elegans</em>, <em>D. melanogaster</em>). However, zebrafish (<em>Danio rerio</em>) have retained AP-4 and can serve as an important model system for studying both the nervous system and overall development. We undertook gene editing in zebrafish using a CRISPR-ExoCas9 knockout system to determine how loss of single AP-4, or its accessory protein tepsin, genes affect embryo development 24 h post-fertilization (hpf). Single gene-edited embryos display abnormal head morphology and neural necrosis. We further conducted the first exploration of how AP-4 single gene knockouts in zebrafish embryos affect expression levels and patterns of two autophagy genes, <em>atg9a</em> and <em>map1lc3b</em>. This work suggests zebrafish may be further adapted and developed as a tool to uncover AP-4 function in membrane trafficking and autophagy in the context of a model organism.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100945"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174139","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}

引用次数: 1