Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressor

Mori, S.Bernardi, R.Laurent, A.Resnati, M.Crippa, A.Gabrieli, A.Keough, R.Gonda, T.Blasi, F.Plow, E.2015-09-302015-09-302012PLoS ONE, 2012; 7(10):e39723-1-e39723-141932-62031932-6203http://hdl.handle.net/2440/94805MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation via acetylation. However little further information is available as to its function. Here we report that MYBBP1A is developmentally essential in the mouse prior to blastocyst formation. In cell culture, down-regulation of MYBBP1A decreases the growth rate of wild type mouse embryonic stem cells, mouse embryo fibroblasts (MEFs) and of human HeLa cells, where it also promotes apoptosis. HeLa cells either arrest at G2/M or undergo delayed and anomalous mitosis. At mitosis, MYBBP1A is localized to a parachromosomal region and gene-expression profiling shows that its down-regulation affects genes controlling chromosomal segregation and cell cycle. However, MYBBP1A down-regulation increases the growth rate of the immortalized NIH3T3 cells. Such Mybbp1a down-regulated NIH3T3 cells are more susceptible to Ras-induced transformation and cause more potent Ras-driven tumors. We conclude that MYBBP1A is an essential gene with novel roles at the pre-mitotic level and potential tumor suppressor activity.en© Mori et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Cells, CulturedHela CellsNIH 3T3 CellsFibroblastsAnimalsMice, Inbred C57BLMice, KnockoutHumansMiceMice, NudeCell Transformation, NeoplasticCarrier ProteinsNucleocytoplasmic Transport ProteinsRNA-Binding ProteinsDNA-Binding ProteinsTumor Suppressor ProteinsNuclear ProteinsTranscription FactorsCell CycleMitosisApoptosisCell ProliferationGene Expression Regulation, DevelopmentalRNA InterferencePregnancyFemaleMaleEmbryonic Stem CellsEmbryo, MammalianHEK293 CellsMyb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressorJournal article003002655910.1371/journal.pone.00397230003098315000022-s2.0-84867313127107745Gonda, T. [0000-0002-8792-3021]