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

被引:36
作者
Mori, Silvia [1 ]
Bernardi, Rosa [1 ,2 ]
Laurent, Audrey [3 ]
Resnati, Massimo [2 ]
Crippa, Ambra [2 ]
Gabrieli, Arianna [3 ]
Keough, Rebecca [4 ,6 ,7 ]
Gonda, Thomas J. [5 ,6 ,7 ]
Blasi, Francesco [1 ,3 ]
机构
[1] Univ Vita Salute San Raffaele, Milan, Italy
[2] Ist Sci San Raffaele, I-20132 Milan, Italy
[3] Fdn Ist FIRC Oncol Mol IFOM, Milan, Italy
[4] Flinders Univ S Australia, Adelaide, SA 5001, Australia
[5] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia
[6] Inst Med & Vet Sci, Div Human Immunol, Adelaide, SA 5000, Australia
[7] Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5000, Australia
来源
PLOS ONE | 2012年 / 7卷 / 10期
基金
英国医学研究理事会;
关键词
FALSE DISCOVERY RATE; PREP1; P53; NUCLEOLUS; NORMALIZATION; ACETYLATION; REPRESSOR; SUMMARIES; P38;
D O I
10.1371/journal.pone.0039723
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:14
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