CCNE1 and E2F1 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 CDKN1B and its C-terminal truncated form, namely p27*, which is translate...

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Autores principales:	Kei Kikuchi, Daisuke Kaida
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pre-mRNA splicing spliceostatin A cell cycle G1 phase cyclin E E2F1 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/cddfb050680e47229d9dd0938f687848
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spelling	oai:doaj.org-article:cddfb050680e47229d9dd0938f6878482021-11-11T17:06:06Z<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment10.3390/ijms2221116231422-00671661-6596https://doaj.org/article/cddfb050680e47229d9dd0938f6878482021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11623https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Kei KikuchiDaisuke KaidaMDPI AGarticlepre-mRNA splicingspliceostatin Acell cycleG1 phasecyclin EE2F1Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11623, p 11623 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pre-mRNA splicing spliceostatin A cell cycle G1 phase cyclin E E2F1 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	pre-mRNA splicing spliceostatin A cell cycle G1 phase cyclin E E2F1 Biology (General) QH301-705.5 Chemistry QD1-999 Kei Kikuchi Daisuke Kaida <i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
description	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.
format	article
author	Kei Kikuchi Daisuke Kaida
author_facet	Kei Kikuchi Daisuke Kaida
author_sort	Kei Kikuchi
title	<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
title_short	<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
title_full	<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
title_fullStr	<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
title_full_unstemmed	<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment
title_sort	<i>ccne1</i> and <i>e2f1</i> partially suppress g1 phase arrest caused by spliceostatin a treatment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cddfb050680e47229d9dd0938f687848
work_keys_str_mv	AT keikikuchi iccne1iandie2f1ipartiallysuppressg1phasearrestcausedbyspliceostatinatreatment AT daisukekaida iccne1iandie2f1ipartiallysuppressg1phasearrestcausedbyspliceostatinatreatment
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<i>CCNE1</i> and <i>E2F1</i> Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

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