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Steroidogenic acute regulatory protein (StAR) controls a rate-limiting step in steroid biosynthesis, yet its regulatory mechanism in E2 production is incompletely understood. This study identifies StAR as an acetylated protein and maps acetylated lysine residues by LC-MS/MS, showing that acetylation sites and HDAC inhibitor responses modulate E2 synthesis. Site-directed StAR acetylation mimetics (K111Q, K253Q) increase E2 in ER+ and triple-negative cells, while deacetylation mutants (K111R, K253R) reduce E2 biosynthesis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/acetylation-of-steroidogenic-acute-regulatory-protein-sensitizes-17-estradiol-regulation-in-hormone-sensitive-breast-cancer-cells/328695/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/acetylation-of-steroidogenic-acute-regulatory-protein-sensitizes-17-estradiol-regulation-in-hormone-sensitive-breast-cancer-cells/328695.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the study’s central focus regarding breast cancer cells?","Question",{"text":112,"@type":113},"The study examines how acetylation of steroidogenic acute regulatory protein (StAR) sensitizes regulation of 17β-estradiol in hormone-sensitive breast cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers identify acetylated StAR residues?",{"text":117,"@type":113},"They discovered StAR as an acetylated protein and used LC-MS/MS to identify lysine residues that are putatively acetylated in malignant and non-malignant breast cells.",{"name":119,"@type":110,"acceptedAnswer":120},"How do StAR acetylation mimetics and deacetylation mutants affect E2 levels?",{"text":121,"@type":113},"K111Q and K253Q acetylation mimetic mutants increase E2 levels in ER+ MCF7 and triple-negative MB-231 cells, whereas K111R and K253R deacetylation mutants diminish E2 biosynthesis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},328695,1790128181,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Communication  \nAcetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17β-Estradiol Regulation in Hormone-Sensitive Breast  \nCancer Cells  \nPulak R. Manna 1, *, Deborah Molehin 2, Ahsen U. Ahmed 3, Shengping Yang 4  \nand P. Hemachandra Reddy 1,5,6,7,8  \nCitation: Manna, P.R.; Molehin, D.; Ahmed, A.U.; Yang, S.; Reddy, P.H. Acetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17β-Estradiol Regulation in Hormone-Sensitive Breast Cancer Cells. Int. J. Mol. Sci. 2024, 25, 8732 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25168732  \nAcademic Editor: Juan A. Rosado  \nReceived: 18 July 2024  \nRevised: 8 August 2024  \nAccepted: 8 August 2024  \nPublished: 10 August 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; [hemachandra.reddy@ttuhsc.edu](hemachandra.reddy@ttuhsc.edu)  \n2 College of Veterinary Medicine, Midwestern University, Glendale, AZ 85308, USA; [dmoleh@midwestern.edu](dmoleh@midwestern.edu)  \n3 Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA; [ahsen.ahmeda@ttuhsc.edu](ahsen.ahmeda@ttuhsc.edu)  \n4 Department of Biostatistics, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA; [shengping.yang@pbrc.edu](shengping.yang@pbrc.edu)  \n5 Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA  \n6 Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA  \n7 Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA  \n8 Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA  \n* [Correspondence: pulak.manna@ttuhsc.edu](Correspondence: pulak.manna@ttuhsc.edu); Tel.: +1-806-743-3573; Fax: +1-806-743-2334  \nAbstract: An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2) . The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography–tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their va","cbCaigeqiak5TYDy","https://ap.wps.com/l/cbCaigeqiak5TYDy","pdf",1973376,15,"English","# Introduction\n## Breast cancer subtypes and estrogen signaling\n## Aromatase and estrogen biosynthesis in breast tissue","[{\"question\":\"What is the study’s central focus regarding breast cancer cells?\",\"answer\":\"The study examines how acetylation of steroidogenic acute regulatory protein (StAR) sensitizes regulation of 17β-estradiol in hormone-sensitive breast cancer cells.\"},{\"question\":\"How did the researchers identify acetylated StAR residues?\",\"answer\":\"They discovered StAR as an acetylated protein and used LC-MS/MS to identify lysine residues that are putatively acetylated in malignant and non-malignant breast cells.\"},{\"question\":\"How do StAR acetylation mimetics and deacetylation mutants affect E2 levels?\",\"answer\":\"K111Q and K253Q acetylation mimetic mutants increase E2 levels in ER+ MCF7 and triple-negative MB-231 cells, whereas K111R and K253R deacetylation mutants diminish E2 biosynthesis.\"}]","Acetylation of Steroidogenic Acute Regulatory Protein Sensitizes 17β-Estradiol Regulation in Hormone-Sensitive Breast Cancer Cells | PDF",1789980594,38]