2024-03-29T15:07:07Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1645602020-12-13T09:15:56Zcom_10261_3284com_10261_1col_10261_3285
2018-05-08T12:45:47Z
urn:hdl:10261/164560
MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis
Lafita, M. Carmen
Blanco, Rosa
Mata-Garrido, Jorge
Liaño-Pons, Judith
Tapia, Olga
García-Gutiérrez, Lucía
García-Alegría, Eva
Berciano, María T.
Lafarga, Miguel
León, Javier
Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
European Commission
Nucleolus
Transcription regulation
Pre-rRNA
UBF
MXD1
MXD1 is a protein that interacts with MAX, to form a repressive transcription factor. MXD1-MAX binds E-boxes. MXD1-MAX antagonizes the transcriptional activity of the MYC oncoprotein in most models. It has been reported that MYC overexpression leads to augmented RNA synthesis and ribosome biogenesis, which is a relevant activity in MYC-mediated tumorigenesis. Here we describe that MXD1, but not MYC or MNT, localizes to the nucleolus in a wide array of cell lines derived from different tissues (carcinoma, leukemia) as well as in embryonic stem cells. MXD1 also localizes in the nucleolus of primary tissue cells as neurons and Sertoli cells. The nucleolar localization of MXD1 was confirmed by co-localization with UBF. Co-immunoprecipitation experiments showed that MXD1 interacted with UBF and proximity ligase assays revealed that this interaction takes place in the nucleolus. Furthermore, chromatin immunoprecipitation assays showed that MXD1 was bound in the transcribed rDNA chromatin, where it co-localizes with UBF, but also in the ribosomal intergenic regions. The MXD1 involvement in rRNA synthesis was also suggested by the nucleolar segregation upon rRNA synthesis inhibition by actinomycin D. Silencing of MXD1 with siRNAs resulted in increased synthesis of pre-rRNA while enforced MXD1 expression reduces it. The results suggest a new role for MXD1, which is the control of ribosome biogenesis. This new MXD1 function would be important to curb MYC activity in tumor cells.
2018-05-08T12:45:47Z
2018-05-08T12:45:47Z
2016
2018-05-08T12:45:47Z
artículo
Oncotarget 7(43): 69536-69548 (2016)
http://hdl.handle.net/10261/164560
10.18632/oncotarget.11766
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100003329
27588501
eng
Publisher's version
https://doi.org/10.18632/oncotarget.11766
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2014-54754-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-53526-R
http://creativecommons.org/licenses/by/3.0/
openAccess
Impact Journals