000136326 001__ 136326
000136326 005__ 20240829112947.0
000136326 0247_ $$2doi$$a10.1093/nar/gkae564
000136326 0248_ $$2sideral$$a139232
000136326 037__ $$aART-2024-139232
000136326 041__ $$aeng
000136326 100__ $$aBaños-Jaime, Blanca
000136326 245__ $$aPhosphorylation at the disordered N-end makes HuR accumulate and dimerize in the cytoplasm
000136326 260__ $$c2024
000136326 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136326 5203_ $$aHuman antigen R (HuR) is an RNA binding protein mainly involved in maintaining the stability and controlling the translation of mRNAs, critical for immune response, cell survival, proliferation and apoptosis. Although HuR is a nuclear protein, its mRNA translational-related function occurs at the cytoplasm, where the oligomeric form of HuR is more abundant. However, the regulation of nucleo-cytoplasmic transport of HuR and its connection with protein oligomerization remain unclear. In this work, we describe the phosphorylation of Tyr5 as a new hallmark for HuR activation. Our biophysical, structural and computational assays using phosphorylated and phosphomimetic HuR proteins demonstrate that phosphorylation of Tyr5 at the disordered N-end stretch induces global changes on HuR dynamics and conformation, modifying the solvent accessible surface of the HuR nucleo-cytoplasmic shuttling (HNS) sequence and releasing regions implicated in HuR dimerization. These findings explain the preferential cytoplasmic accumulation of phosphorylated HuR in HeLa cells, aiding to comprehend the mechanisms underlying HuR nucleus-cytoplasm shuttling and its later dimerization, both of which are relevant in HuR-related pathogenesis.
000136326 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-117116RP$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-126663NB-I00
000136326 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000136326 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000136326 700__ $$aCorrales-Guerrero, Laura
000136326 700__ $$aPérez-Mejías, Gonzalo
000136326 700__ $$aRejano-Gordillo, Claudia M
000136326 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000136326 700__ $$aMartínez-Cruz, Luis Alfonso
000136326 700__ $$aMartínez-Chantar, María Luz
000136326 700__ $$aDe la Rosa, Miguel A
000136326 700__ $$aDíaz-Moreno, Irene
000136326 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000136326 773__ $$g52, 14 (2024), 8552–8565$$pNucleic acids res.$$tNucleic Acids Research$$x0305-1048
000136326 8564_ $$s9079482$$uhttps://zaguan.unizar.es/record/136326/files/texto_completo.pdf$$yVersión publicada
000136326 8564_ $$s2549000$$uhttps://zaguan.unizar.es/record/136326/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000136326 909CO $$ooai:zaguan.unizar.es:136326$$particulos$$pdriver
000136326 951__ $$a2024-08-29-11:26:06
000136326 980__ $$aARTICLE