Università Vita Salute San Raffaele, Milan, Italy.
PLoS One. 2012;7(10):e39723. doi: 10.1371/journal.pone.0039723. Epub 2012 Oct 8.
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.
MYBBP1A 是一种主要位于核仁的转录调控因子,通过乙酰化参与 rDNA 合成和 p53 激活。然而,关于其功能的进一步信息较少。在这里,我们报告 MYBBP1A 在小鼠胚胎囊胚形成之前的发育过程中是必不可少的。在细胞培养中,下调 MYBBP1A 会降低野生型小鼠胚胎干细胞、小鼠胚胎成纤维细胞 (MEFs) 和人 HeLa 细胞的生长速度,同时促进细胞凋亡。HeLa 细胞要么在 G2/M 期停滞,要么经历延迟和异常有丝分裂。在有丝分裂过程中,MYBBP1A 定位于副染色质区域,基因表达谱显示其下调会影响控制染色体分离和细胞周期的基因。然而,下调 MYBBP1A 会增加永生化 NIH3T3 细胞的生长速度。这种 Mybbp1a 下调的 NIH3T3 细胞对 Ras 诱导的转化更敏感,并导致更有效的 Ras 驱动的肿瘤。我们得出结论,MYBBP1A 是一种必需基因,在有丝分裂前水平具有新的作用,并具有潜在的肿瘤抑制活性。