{"title":"组蛋白伴侣 APLF 的激酶活性可维持小鼠胚胎干细胞中心体的稳定状态。","authors":"Sruthy Manuraj Rajam , Pallavi Chinnu Varghese , Mayur Balkrishna Shirude , Khaja Mohieddin Syed , Anjali Devarajan , Kathiresan Natarajan , Debasree Dutta","doi":"10.1016/j.ejcb.2024.151439","DOIUrl":null,"url":null,"abstract":"<div><p>Our recent studies revealed the role of mouse Aprataxin PNK-like Factor (APLF) in development. Nevertheless, the comprehensive characterization of mouse APLF remains entirely unexplored. Based on domain deletion studies, here we report that mouse APLF's Acidic Domain and Fork Head Associated (FHA) domain can chaperone histones and repair DNA like the respective human orthologs. Immunofluorescence studies in mouse embryonic stem cells showed APLF co-localized with γ-tubulin within and around the centrosomes and govern the number and integrity of centrosomes via PLK4 phosphorylation. Enzymatic analysis established mouse APLF as a kinase. Docking studies identified three putative ATP binding sites within the FHA domain. Site-directed mutagenesis showed that R37 residue within the FHA domain is indispensable for the kinase activity of APLF thereby regulating the centrosome number. These findings might assist us comprehend APLF in different pathological and developmental conditions and reveal non-canonical kinase activity of proteins harbouring FHA domains that might impact multiple cellular processes.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151439"},"PeriodicalIF":4.5000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000566/pdfft?md5=f9b67a2e63edf7473ac1ba067f0da878&pid=1-s2.0-S0171933524000566-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Kinase activity of histone chaperone APLF maintains steady state of centrosomes in mouse embryonic stem cells\",\"authors\":\"Sruthy Manuraj Rajam , Pallavi Chinnu Varghese , Mayur Balkrishna Shirude , Khaja Mohieddin Syed , Anjali Devarajan , Kathiresan Natarajan , Debasree Dutta\",\"doi\":\"10.1016/j.ejcb.2024.151439\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Our recent studies revealed the role of mouse Aprataxin PNK-like Factor (APLF) in development. Nevertheless, the comprehensive characterization of mouse APLF remains entirely unexplored. Based on domain deletion studies, here we report that mouse APLF's Acidic Domain and Fork Head Associated (FHA) domain can chaperone histones and repair DNA like the respective human orthologs. Immunofluorescence studies in mouse embryonic stem cells showed APLF co-localized with γ-tubulin within and around the centrosomes and govern the number and integrity of centrosomes via PLK4 phosphorylation. Enzymatic analysis established mouse APLF as a kinase. Docking studies identified three putative ATP binding sites within the FHA domain. Site-directed mutagenesis showed that R37 residue within the FHA domain is indispensable for the kinase activity of APLF thereby regulating the centrosome number. These findings might assist us comprehend APLF in different pathological and developmental conditions and reveal non-canonical kinase activity of proteins harbouring FHA domains that might impact multiple cellular processes.</p></div>\",\"PeriodicalId\":12010,\"journal\":{\"name\":\"European journal of cell biology\",\"volume\":\"103 3\",\"pages\":\"Article 151439\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-06-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0171933524000566/pdfft?md5=f9b67a2e63edf7473ac1ba067f0da878&pid=1-s2.0-S0171933524000566-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of cell biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0171933524000566\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of cell biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171933524000566","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Kinase activity of histone chaperone APLF maintains steady state of centrosomes in mouse embryonic stem cells
Our recent studies revealed the role of mouse Aprataxin PNK-like Factor (APLF) in development. Nevertheless, the comprehensive characterization of mouse APLF remains entirely unexplored. Based on domain deletion studies, here we report that mouse APLF's Acidic Domain and Fork Head Associated (FHA) domain can chaperone histones and repair DNA like the respective human orthologs. Immunofluorescence studies in mouse embryonic stem cells showed APLF co-localized with γ-tubulin within and around the centrosomes and govern the number and integrity of centrosomes via PLK4 phosphorylation. Enzymatic analysis established mouse APLF as a kinase. Docking studies identified three putative ATP binding sites within the FHA domain. Site-directed mutagenesis showed that R37 residue within the FHA domain is indispensable for the kinase activity of APLF thereby regulating the centrosome number. These findings might assist us comprehend APLF in different pathological and developmental conditions and reveal non-canonical kinase activity of proteins harbouring FHA domains that might impact multiple cellular processes.
期刊介绍：
The European Journal of Cell Biology, a journal of experimental cell investigation, publishes reviews, original articles and short communications on the structure, function and macromolecular organization of cells and cell components. Contributions focusing on cellular dynamics, motility and differentiation, particularly if related to cellular biochemistry, molecular biology, immunology, neurobiology, and developmental biology are encouraged. Manuscripts describing significant technical advances are also welcome. In addition, papers dealing with biomedical issues of general interest to cell biologists will be published. Contributions addressing cell biological problems in prokaryotes and plants are also welcome.
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