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We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-\/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20\u00a0min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.<\/jats:p>","DOI":"10.1007\/s13402-023-00911-9","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T05:02:12Z","timestamp":1703653332000},"page":"1065-1070","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor"],"prefix":"10.1007","volume":"47","author":[{"given":"Mickael","family":"Diallo","sequence":"first","affiliation":[]},{"given":"Constan\u00e7a","family":"Pimenta","sequence":"additional","affiliation":[]},{"given":"Fernanda","family":"Murtinheira","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Martins-Alves","sequence":"additional","affiliation":[]},{"given":"Francisco R.","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 Abrantes","family":"da Costa","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Letra-Vilela","sequence":"additional","affiliation":[]},{"given":"Vanesa","family":"Martin","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Rodriguez","sequence":"additional","affiliation":[]},{"given":"M\u00e1rio S.","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Herrera","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"key":"911_CR1","doi-asserted-by":"publisher","unstructured":"J. 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