A novel role of MNT as a negative regulator of REL and the NF-κB pathway

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  • dc.contributor.author Liaño-Pons, Judit
  • dc.contributor.author Lafita-Navarro, M. Carmen
  • dc.contributor.author García-Gaipo, Lorena
  • dc.contributor.author Colomer Montañà, Carlota, 1990-
  • dc.contributor.author Rodríguez, Javier
  • dc.contributor.author von Kriegsheim, Alex
  • dc.contributor.author Hurlin, Peter J.
  • dc.contributor.author Ourique, Fabiana
  • dc.contributor.author Delgado, M. Dolores
  • dc.contributor.author Bigas Salvans, Anna
  • dc.contributor.author Espinosa Blay, Lluís
  • dc.contributor.author León, Javier
  • dc.date.accessioned 2022-01-27T07:45:52Z
  • dc.date.available 2022-01-27T07:45:52Z
  • dc.date.issued 2021
  • dc.description.abstract MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix-loop-helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT-REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT-REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Liaño-Pons J, Lafita-Navarro MC, García-Gaipo L, Colomer C, Rodríguez J, von Kriegsheim A, et al. A novel role of MNT as a negative regulator of REL and the NF-κB pathway. Oncogenesis. 2021 Jan 8; 10(1): 5. DOI: 10.1038/s41389-020-00298-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41389-020-00298-4
  • dc.identifier.issn 2157-9024
  • dc.identifier.uri http://hdl.handle.net/10230/52334
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-88026-R
  • dc.rights Copyright © The Author(s) 2021, corrected publication 2021. 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 from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Proteïnes
  • dc.subject.other Molècules
  • dc.subject.other Càncer--Aspectes genètics
  • dc.title A novel role of MNT as a negative regulator of REL and the NF-κB pathway
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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