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

Authors :
Lluis Espinosa
Alex von Kriegsheim
Anna Bigas
Javier Rodriguez
M. Dolores Delgado
Judit Liaño-Pons
Javier León
Peter J. Hurlin
M. Carmen Lafita-Navarro
Lorena García-Gaipo
Carlota Colomer
Fabiana Ourique
Source :
Oncogenesis, Oncogenesis, Vol 10, Iss 8, Pp 1-1 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group UK, 2021.

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.

Details

Language :
English
ISSN :
21579024
Volume :
10
Issue :
8
Database :
OpenAIRE
Journal :
Oncogenesis
Accession number :
edsair.doi.dedup.....9cae08ed1e2f5ba9e593ffe3b8611712