Expression of the tumor-expressed protein MageB2 enhances rRNA transcription.

Autor: Ladelfa MF; Lab. Oncología Molecular, Departamento de Química Biológica, IQUIBICEN-UBA/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Peche LY; Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Trieste, Italy., Amato GE; Lab. Oncología Molecular, Departamento de Química Biológica, IQUIBICEN-UBA/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Escalada MC; Lab. Oncología Molecular, Departamento de Química Biológica, IQUIBICEN-UBA/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Zampieri S; Centro di Coordinamento Regionale per le Malattie Rare, Ospedale Universitario Santa Maria Della Misericordia, Udine, Italy., Pascucci FA; Lab. Oncología Molecular, Departamento de Química Biológica, IQUIBICEN-UBA/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina., Benevento AF; Plataforma de Bioinformática Argentina, Instituto de Cálculo, Pabellón 2, Ciudad Universitaria, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina., Do Porto DF; Plataforma de Bioinformática Argentina, Instituto de Cálculo, Pabellón 2, Ciudad Universitaria, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina., Dardis A; Centro di Coordinamento Regionale per le Malattie Rare, Ospedale Universitario Santa Maria Della Misericordia, Udine, Italy., Schneider C; Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie, Area Science Park, Trieste, Italy; Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, p.le Kolbe 4, Udine, Italy., Monte M; Lab. Oncología Molecular, Departamento de Química Biológica, IQUIBICEN-UBA/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: mmonte@qb.fcen.uba.ar.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2021 Jun; Vol. 1868 (7), pp. 119015. Date of Electronic Publication: 2021 Mar 17.
DOI: 10.1016/j.bbamcr.2021.119015
Abstrakt: An essential requirement for cells to sustain a high proliferating rate is to be paired with enhanced protein synthesis through the production of ribosomes. For this reason, part of the growth-factor signaling pathways, are devoted to activate ribosome biogenesis. Enhanced production of ribosomes is a hallmark in cancer cells, which is boosted by different mechanisms. Here we report that the nucleolar tumor-protein MageB2, whose expression is associated with cell proliferation, also participates in ribosome biogenesis. Studies carried out in both siRNA-mediated MageB2 silenced cells and CRISPR/CAS9-mediated MageB2 knockout (KO) cells showed that its expression is linked to rRNA transcription increase independently of the cell proliferation status. Mechanistically, MageB2 interacts with phospho-UBF, a protein which causes the recruitment of RNA Pol I pre-initiation complex required for rRNA transcription. In addition, cells expressing MageB2 displays enhanced phospho-UBF occupancy at the rDNA gene promoter. Proteomic studies performed in MageB2 KO cells revealed impairment in ribosomal protein (RPs) content. Functionally, enhancement in rRNA production in MageB2 expressing cells, was directly associated with an increased dynamic in protein synthesis. Altogether our results unveil a novel function for a tumor-expressed protein from the MAGE-I family. Findings reported here suggest that nucleolar MageB2 might play a role in enhancing ribosome biogenesis as part of its repertoire to support cancer cell proliferation.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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