{"title":"Identification and characterisation of a novel interaction between oestrogen receptor alpha and FOXP2","authors":"Aasiya Lakhi, Sylvia Fanucchi","doi":"10.1016/j.biochi.2024.01.014","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α<span><span> (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. </span>Isothermal titration calorimetry and </span></span>fluorescence anisotropy<span> were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found </span></span><em>in vivo</em>. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"221 ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimie","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0300908424000324","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. Isothermal titration calorimetry and fluorescence anisotropy were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found in vivo. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies.
期刊介绍:
Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English.
Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.