A-MYB substitutes for B-MYB in activating cell cycle genes and in stimulating proliferation.
| Autor: | Kohler R; Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103 Leipzig, Germany., Engeland K; Molecular Oncology, Medical School, University of Leipzig, Semmelweisstr. 14, 04103 Leipzig, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | Nucleic acids research [Nucleic Acids Res] 2024 Jul 08; Vol. 52 (12), pp. 6830-6849. |
| DOI: | 10.1093/nar/gkae370 |
| Abstrakt: | A-MYB (MYBL1) is a transcription factor with a role in meiosis in spermatocytes. The related B-MYB protein is a key oncogene and a master regulator activating late cell cycle genes. To activate genes, B-MYB forms a complex with MuvB and is recruited indirectly to cell cycle genes homology region (CHR) promoter sites of target genes. Activation through the B-MYB-MuvB (MMB) complex is essential for successful mitosis. Here, we discover that A-MYB has a function in transcriptional regulation of the mitotic cell cycle and can substitute for B-MYB. Knockdown experiments in cells not related to spermatogenesis show that B-MYB loss alone merely delays cell cycle progression. Only dual knockdown of B-MYB and A-MYB causes G2/M cell cycle arrest, endoreduplication, and apoptosis. A-MYB can substitute for B-MYB in binding to MuvB. The resulting A-MYB-MuvB complex activates genes through CHR sites. We find that A-MYB activates the same target genes as B-MYB. Many of the corresponding proteins are central regulators of the cell division cycle. In summary, we demonstrate that A-MYB is an activator of the mitotic cell cycle by activating late cell cycle genes. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
| Databáze: | MEDLINE |
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