{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:51:31Z","timestamp":1791229891559,"version":"4.1.0"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish State Research Agency","award":["PID2021-126663NB-I00"],"award-info":[{"award-number":["PID2021-126663NB-I00"]}],"id":[{"id":"https:\/\/ror.org\/003x0zc53","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Spanish State Research Agency","award":["PID2024-157414NB-I00"],"award-info":[{"award-number":["PID2024-157414NB-I00"]}],"id":[{"id":"https:\/\/ror.org\/003x0zc53","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Spanish State Research Agency","award":["PRE2019-091404"],"award-info":[{"award-number":["PRE2019-091404"]}],"id":[{"id":"https:\/\/ror.org\/003x0zc53","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ramon Areces Foundation","award":["LEUCYTO-FRA2025-MAR"],"award-info":[{"award-number":["LEUCYTO-FRA2025-MAR"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:p>\n                    Nucleophosmin (NPM1) is a multifunctional nucleolar protein essential for ribosome biogenesis, genome stability, and stress responses. Its integration into the nucleolus depends on its oligomerization and multivalent interactions that enable liquid\u2013liquid phase separation (LLPS). Here, we investigate how tyrosine phosphorylation at Tyr17, Tyr29, and Tyr67 located within the interface between monomers at the N-terminal oligomerization domain regulates NPM1 structure and function. Replacing tyrosines with\n                    <jats:italic toggle=\"yes\">p-<\/jats:italic>\n                    carboxymethyl-L-phenylalanine as phosphomimetic substitutions, we show that phosphorylation at Tyr17 and Tyr67 disrupts key intermonomer interactions and destabilizes the NPM1 pentameric assembly, which drives an order-to-disorder transition and impairs binding to nuclear partners. Consequently, dual phosphorylation at Tyr17 and Tyr67 disturbs both homotypic and heterotypic LLPS, thereby impairing incorporation of NPM1 into the nucleolus. This altered localization of NPM1 serves as a hallmark of p53 activation, driven both by nucleoplasmic NPM1 and by the release of ARF from NPM1-dependent sequestration in the nucleolus. Altogether, our results provide a molecular mechanistic explanation on how phosphorylation-induced structural and dynamic changes drive the release of NPM1 from the nucleolus under genotoxic stress.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2533263123","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:03:46Z","timestamp":1791227026000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Tyrosine phosphorylation unfolds nucleophosmin and disrupts its integration into the nucleolus"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-7916","authenticated-orcid":false,"given":"Rafael L.","family":"Giner-Arroyo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfc7t72","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Chemical Research \u2013 Scientific Research Center \u201cIsla de la Cartuja\u201d 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