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MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis

Abstract: 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.

 Fuente: Oncotarget, 2016, 7(43), 69536-69548

 Publisher: Impact Journals

 Year of publication: 2016

 No. of pages: 13

 Publication type: Article

 DOI: 10.18632/oncotarget.11766

 ISSN: 1949-2553

 Spanish project: SAF2014-53526, BFU2014-54754P,RETIC-RD012-036-033, CIBERNED CB06/05/0037

 Publication Url: https://doi.org/10.18632/oncotarget.11766

Authorship

MARIA DEL CARMEN LAFITA NAVARRO

JORGE MATA GARRIDO

JUDIT LIAÑO PONS

OLGA TAPIA MARTINEZ

LUCIA GARCIA GUTIERREZ

EVA GARCIA ALEGRIA

MARIA TERESA BERCIANO BLANCO