<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by <i>CDKN1B</i> and its C-terminal truncated form, namely p27*, which is translate...
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| Autores principales: | , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/cddfb050680e47229d9dd0938f687848 |
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| Sumario: | The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by <i>CDKN1B</i> and its C-terminal truncated form, namely p27*, which is translated from <i>CDKN1B</i> pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including <i>CCNE1</i>, <i>CCNE2</i>, and <i>E2F1</i>, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of <i>CCNE1</i> and <i>E2F1</i> in combination with <i>CDKN1B</i> knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of <i>CCNE1</i> and <i>E2F1</i> contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest. |
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