MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis
| Autor: | Maria del Carmen Lafita-Navarro, Javier León, Miguel Lafarga, Olga Tapia, Eva Garcia-Alegria, Judit Liaño-Pons, Maria T. Berciano, Rosa M. Blanco, Lucía García-Gutiérrez, Jorge Mata-Garrido |
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| Přispěvatelé: | Universidad de Cantabria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Small interfering RNA Immunoprecipitation Nucleolus pre-rRNA Ribosome biogenesis Biology 03 medical and health sciences UBF MXD1 Transcriptional regulation Animals Humans nucleolus Transcription factor Cells Cultured Neurons Manchester Cancer Research Centre Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ResearchInstitutes_Networks_Beacons/mcrc Transcription regulation Molecular biology Spermatogonia Rats Chromatin Repressor Proteins HEK293 Cells 030104 developmental biology Oncology RNA Ribosomal Pre-rRNA RNA Interference transcription regulation K562 Cells Pol1 Transcription Initiation Complex Proteins Chromatin immunoprecipitation Cell Nucleolus Research Paper HeLa Cells Protein Binding |
| Zdroj: | Oncotarget Oncotarget. 2016 Aug 31 Lafita-Navarro, M D C, Blanco, R, Mata-Garrido, J, Liaño-Pons, J, Tapia, O, García-Gutiérrez, L, García-Alegría, E, Berciano, M T, Lafarga, M & León, J 2016, ' MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis ', Oncotarget, vol. 7, no. 43, pp. 69536-69548 . https://doi.org/10.18632/oncotarget.11766 UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11766 |
| Popis: | 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. The work was supported by grants SAF2014-53526 (to JL), BFU2014-54754P (to ML and MTB) from Spanish Economy and Competitiveness Ministry (MINECO), and grants RETIC-RD012-036-033 (to JL) and CIBERNED CB06/05/0037 (to ML) from Instituto Carlos III to JL. These funding were co-sponsored by the FEDER program. MCL was recipient of a fellowship from the FPU program from MINECO. |
| Databáze: | OpenAIRE |
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