Myb-Binding Protein 1A (MYBBP1A) Is Essential for Early Embryonic Development, Controls Cell Cycle and Mitosis, and Acts as a Tumor Suppressor

Abstract

MYBBP1A 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.

Fragmentation of human cleavage-stage embryos is related to the progression through meiotic and mitotic cell cycles

“…mediator of sister chromatid cohesion, DNA double-strand break repair, and transcriptional control (43). MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation and which may affect genes controlling chromosomal segregation and cell cycle (44).…”

TPPII, MYBBP1A and CDK2 form a protein–protein interaction network

“…However in our experimental study gene expression of p21 was not affected by changes in TPPII and MYBBP1A gene expressions. According to Mori et al [14], MYBBP1A down-regulation causes growth inhibition in HeLa cells, cell cycle arrest at G2/ M phase of the cell cycle with certain effects at the G1/S phase and mitotic aberrations. However, the opposite effect of MYBBP1A has been observed in the immortalized cell line NIH3T3, where cell growth stimulation was detected upon MYBBP1A depletion [14].…”

“…According to Mori et al [14], MYBBP1A down-regulation causes growth inhibition in HeLa cells, cell cycle arrest at G2/ M phase of the cell cycle with certain effects at the G1/S phase and mitotic aberrations. However, the opposite effect of MYBBP1A has been observed in the immortalized cell line NIH3T3, where cell growth stimulation was detected upon MYBBP1A depletion [14]. According to our study, upregulation of TPPII in HEK293 cells causes downregulation of MYBBP1a during cell detachment.…”

Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates

“…Hence, in the absence of PREP1, MYBBP1A fails to inhibit the transcriptional activity of PGC1A in muscle cells, increasing insulin sensitivity (Oriente et al, 2008). MYBBP1A acts as a tumor suppressor and its down-regulation in HeLa cells leads to drastic mitotic abnormalities, a block in G2/M, and increased sensitivity to oncogenic transformation (Mori et al, 2012). …”