title: 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.
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.|Present address: Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors: Maria Del Carmen
authors: MC
authors: Lafita-Navarro
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors: Rosa
authors: R
authors: Blanco
authors: Department of Anatomy and Cell Biology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, Santander, Spain.
authors: Jorge
authors: J
authors: Mata-Garrido
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors: Judit
authors: J
authors: Liaño-Pons
authors: Department of Anatomy and Cell Biology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, Santander, Spain.
authors: Olga
authors: O
authors: Tapia
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors: Lucía
authors: L
authors: García-Gutiérrez
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.|Present address: Stem Cell Hematopoiesis Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
authors: Eva
authors: E
authors: García-Alegría
authors: Department of Anatomy and Cell Biology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, Santander, Spain.
authors: María T
authors: MT
authors: Berciano
authors: Department of Anatomy and Cell Biology and Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Cantabria-IDIVAL, Santander, Spain.
authors: Miguel
authors: M
authors: Lafarga
authors: Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de Cantabria, and Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors: Javier
authors: J
authors: León
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D020014:K562 Cells; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C079439:MXD1 protein, human; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D012097:Repressor Proteins; C063844:transcription factor UBF
keywords: MXD1; UBF; nucleolus; pre-rRNA; transcription regulation