Functional preservation of tumor suppressor protein p53 by formation of baicalein-induced higher-order multimers

Functional preservation of tumor suppressor protein p53 by formation of baicalein-induced higher-order multimers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Functional preservation of tumor suppressor protein p53 by formation of baicalein-induced higher-order multimers Reiji Hijikata, Haruna Yoshida, Hidekazu Hiroaki, Emi Hibino This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6652912/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract p53 protein is an important transcription factor for suppressing oncogenesis. p53 is inactivated by the amorphous or amyloid aggregation, mainly via its aggregation-prone p53 DNA-binding domain (p53-DBD). Amyloid-like aggregation inhibition or MDM2-dependent degradation has been well studied, but amorphous aggregation inhibition, which is strongly associated with the loss of DNA-binding ability, has been poorly studied. We evaluated the p53 amorphous aggregation inhibitory activity of 16 flavonoids. As a result, baicalein, known as a flavonoid with anticancer activity, suppresses both the amorphous and amyloid aggregation of p53-DBD. Interestingly, baicalein promoted a higher-order multimer formation without structural transition. The cell-based assays showed an increase in nuclear p53 and activation of the p53 pathway following treatment with baicalein. We hypothesized that baicalein prevents either degradation or inactivation of p53 by promoting the multimer formation of nuclear p53, resulting in the preservation of p53 with transcriptional activity, which is necessary for anticancer activity. Biological sciences/Biochemistry/Proteins/Oncogene proteins Biological sciences/Molecular biology/Protein folding/Protein aggregation Full Text Additional Declarations Yes there is potential Competing Interest. Among the authors, H.H. is the founders of the Nagoya University-based spinoff startup company, BeCellBar LLC. The other authors declare no competing interest related to the content of this article. Supplementary Files NatCommunSupple250509.pdf Supplementary Information nrreportingsummary.pdf Reporting Summary Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6652912","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":456502875,"identity":"f2349ea5-a429-4a8a-a4cb-ea2e1cfaa588","order_by":0,"name":"Reiji Hijikata","email":"","orcid":"","institution":"Nagoya University","correspondingAuthor":false,"prefix":"","firstName":"Reiji","middleName":"","lastName":"Hijikata","suffix":""},{"id":456502876,"identity":"3b3dce3a-f38f-4ff7-976f-cad52a46b692","order_by":1,"name":"Haruna Yoshida","email":"","orcid":"","institution":"Nagoya University","correspondingAuthor":false,"prefix":"","firstName":"Haruna","middleName":"","lastName":"Yoshida","suffix":""},{"id":456502874,"identity":"5fbd4bfc-4120-4085-8045-27574bf271ac","order_by":2,"name":"Hidekazu Hiroaki","email":"","orcid":"","institution":"Nagoya University","correspondingAuthor":false,"prefix":"","firstName":"Hidekazu","middleName":"","lastName":"Hiroaki","suffix":""},{"id":456502873,"identity":"428d7106-3231-4643-a088-4c24369f0151","order_by":3,"name":"Emi Hibino","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-0846-8842","institution":"Nagoya University","correspondingAuthor":true,"prefix":"","firstName":"Emi","middleName":"","lastName":"Hibino","suffix":""}],"badges":[],"createdAt":"2025-05-13 07:55:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6652912/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6652912/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83764812,"identity":"e8c64be5-18a2-401b-9d36-c0a7dfd41ddb","added_by":"auto","created_at":"2025-06-02 10:48:53","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2324301,"visible":true,"origin":"","legend":"Article File","description":"","filename":"NatCommunMain250513.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6652912/v1_covered_9a18f71a-cf12-4802-9b60-91ec349cf5a5.pdf"},{"id":83121045,"identity":"5c051417-306f-4b4f-b4cd-91036d92c98f","added_by":"auto","created_at":"2025-05-20 08:54:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1202661,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"NatCommunSupple250509.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6652912/v1/5338abcfa9277114c80ecdd3.pdf"},{"id":83121042,"identity":"4da0cc01-4787-462d-a4b7-b65a28540727","added_by":"auto","created_at":"2025-05-20 08:54:17","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1667234,"visible":true,"origin":"","legend":"Reporting Summary","description":"","filename":"nrreportingsummary.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6652912/v1/dbd2e7bc28da3d85914fc870.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nAmong the authors, H.H. is the founders of the Nagoya University-based spinoff startup company, BeCellBar LLC. 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