Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.

Authors

Shakur Mohibi, University of Nebraska Medical Center
Channabasavaiah B. Gurumurthy, University of Nebraska Medical CenterFollow
Alo Nag, Northwestern University
Jun Wang, University of Nebraska Medical Center
Sameer Mirza, University of Nebraska Medical CenterFollow
Yousaf Mian, Northwestern University
Meghan Quinn, University of Nebraska Medical Center
Bryan J. Katafiasz, University of Nebraska Medical CenterFollow
James D. Eudy, University of Nebraska Medical CenterFollow
Sanjit Pandey, University of Nebraska Medical CenterFollow
Chittibabu Guda, University of Nebraska Medical CenterFollow
Mayumi Naramura, Northwestern University
Hamid Band, University of Nebraska Medical CenterFollow
Vimla Band, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

The Journal of biological chemistry

Publication Date

Summer 8-24-2012

Volume

287

Abstract

Ada3 protein is an essential component of histone acetyl transferase containing coactivator complexes conserved from yeast to human. We show here that germline deletion of Ada3 in mouse is embryonic lethal, and adenovirus-Cre mediated conditional deletion of Ada3 in Ada3(FL/FL) mouse embryonic fibroblasts leads to a severe proliferation defect which was rescued by ectopic expression of human Ada3. A delay in G(1) to S phase of cell cycle was also seen that was due to accumulation of Cdk inhibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3. We further showed that this defect could be partially reverted by knocking down p27. Additionally, drastic changes in global histone acetylation and changes in global gene expression were observed in microarray analyses upon loss of Ada3. Lastly, formation of abnormal nuclei, mitotic defects and delay in G(2)/M to G(1) transition was seen in Ada3 deleted cells. Taken together, we provide evidence for a critical role of Ada3 in embryogenesis and cell cycle progression as an essential component of HAT complex.

MeSH Headings

Acetylation, Animals, Cell Cycle, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Embryo, Mammalian, Embryonic Development, Fibroblasts, Gene Expression Regulation, Developmental, Histones, Humans, Mice, Mice, Knockout, Transcription Factors

DOI Link

10.1074/jbc.M112.378901

ISSN

1083-351X

Rights

This research was originally published in The Journal of Biological Chemistry. Mohibi S, Gurumurthy CB, Nag A, et al. Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression. The Journal of Biological Chemistry. 2012; 287:29442-56.© the American Society for Biochemistry and Molecular Biology.

Recommended Citation

Mohibi, Shakur; Gurumurthy, Channabasavaiah B.; Nag, Alo; Wang, Jun; Mirza, Sameer; Mian, Yousaf; Quinn, Meghan; Katafiasz, Bryan J.; Eudy, James D.; Pandey, Sanjit; Guda, Chittibabu; Naramura, Mayumi; Band, Hamid; and Band, Vimla, "Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression." (2012). Journal Articles: Genetics, Cell Biology & Anatomy. 25.
https://digitalcommons.unmc.edu/com_gcba_articles/25