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dc.contributor.authorKirsch, Klára
dc.contributor.authorZeke, András
dc.contributor.authorTőke, Orsolya
dc.contributor.authorSok, Péter
dc.contributor.authorSethi, Ashish
dc.contributor.authorSebő, Anna
dc.contributor.authorKumar, Ganesan Senthil
dc.contributor.authorEgri, Péter
dc.contributor.authorPóti, Ádám L
dc.contributor.authorGooley, Paul
dc.contributor.authorPeti, Wolfgang
dc.contributor.authorBento, Isabel
dc.contributor.authorAlexa, Anita
dc.contributor.authorReményi, Attila
dc.date.accessioned2021-05-06T01:25:59Z
dc.date.available2021-05-06T01:25:59Z
dc.date.issued2020-11-13
dc.identifier.citationKirsch, K., Zeke, A., Tőke, O., Sok, P., Sethi, A., Sebő, A., ... & Reményi, A. (2020). Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38. Nature Communications, 11(1), 1-15.en_US
dc.identifier.issn2041-1723
dc.identifier.pmid33188182
dc.identifier.doi10.1038/s41467-020-19582-3
dc.identifier.urihttp://hdl.handle.net/10150/658200
dc.description.abstractTranscription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch differently sensitive to JNK and p38 in vertebrates. Structures of MAPK-TAD complexes and mechanistic modeling of ATF2 TAD phosphorylation in cells suggest that kinase binding motifs and phosphorylation sites line up to maximize MAPK based co-regulation. This study shows how the activity of an ancient transcription controlling phosphoswitch became dependent on the relative flux of upstream signals. The ATF2 transcription factor is phosphorylated by different mitogen-activated protein (MAP) kinases. Here, the authors show that the functionally distinct MAP kinases JNK and p38 control ATF2 through different binding sites and differential phosphorylation, thereby modulating ATF2's sensitivity to the JNK and p38 pathways.en_US
dc.language.isoenen_US
dc.publisherNATURE RESEARCHen_US
dc.rights© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCo-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38en_US
dc.typeArticleen_US
dc.identifier.eissn2041-1723
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen_US
dc.identifier.journalNATURE COMMUNICATIONSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleNature communications
dc.source.volume11
dc.source.issue1
dc.source.beginpage5769
dc.source.endpage
refterms.dateFOA2021-05-06T01:26:01Z
dc.source.countryUnited States
dc.source.countryEngland


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© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.