Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation

Reversible phosphorylation has emerged as an important mechanism for regulating proteasome function in various physiological processes. Essentially all proteasome phosphorylations characterized thus far occur on proteasome holoenzyme or subcomplexes to regulate substrate degradation. Here, we report...

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Autores principales:	Jinyuan Duan, Wenzhu Li, Xin Shu, Bing Yang, Xiangwei He, Xing Guo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cell cycle mitosis proteasome PSMA5/α5 phosphorylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9234c11d0216444abdc2783bed4d2794
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spelling	oai:doaj.org-article:9234c11d0216444abdc2783bed4d27942021-11-25T17:11:15ZConserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation10.3390/cells101130752073-4409https://doaj.org/article/9234c11d0216444abdc2783bed4d27942021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3075https://doaj.org/toc/2073-4409Reversible phosphorylation has emerged as an important mechanism for regulating proteasome function in various physiological processes. Essentially all proteasome phosphorylations characterized thus far occur on proteasome holoenzyme or subcomplexes to regulate substrate degradation. Here, we report a highly conserved phosphorylation that only exists on the unassembled α5 subunit of the proteasome. The modified residue, α5-Ser16, is within a SP motif typically recognized by cyclin-dependent kinases (CDKs). Using a phospho-specific antibody generated against this site, we found that α5-S16 phosphorylation is mitosis-specific in both yeast and mammalian cells. Blocking this site with a S16A mutation caused growth defect and G2/M arrest of the cell cycle. α5-S16 phosphorylation depends on CDK1 activity and is highly abundant in some but not all mitotic cells. Immunoprecipitation and mass spectrometry (IP-MS) studies identified numerous proteins that could interact with phosphorylated α5, including PLK1, a key regulator of mitosis. α5–PLK1 interaction increased upon mitosis and could be facilitated by S16 phosphorylation. CDK1 activation downstream of PLK1 activity was delayed in S16A mutant cells, suggesting an important role of α5-S16 phosphorylation in regulating PLK1 and mitosis. These data have revealed an unappreciated function of “exo-proteasome” phosphorylation of a proteasome subunit and may bring new insights to our understanding of cell cycle control.Jinyuan DuanWenzhu LiXin ShuBing YangXiangwei HeXing GuoMDPI AGarticlecell cyclemitosisproteasomePSMA5/α5phosphorylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3075, p 3075 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell cycle mitosis proteasome PSMA5/α5 phosphorylation Biology (General) QH301-705.5
spellingShingle	cell cycle mitosis proteasome PSMA5/α5 phosphorylation Biology (General) QH301-705.5 Jinyuan Duan Wenzhu Li Xin Shu Bing Yang Xiangwei He Xing Guo Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
description	Reversible phosphorylation has emerged as an important mechanism for regulating proteasome function in various physiological processes. Essentially all proteasome phosphorylations characterized thus far occur on proteasome holoenzyme or subcomplexes to regulate substrate degradation. Here, we report a highly conserved phosphorylation that only exists on the unassembled α5 subunit of the proteasome. The modified residue, α5-Ser16, is within a SP motif typically recognized by cyclin-dependent kinases (CDKs). Using a phospho-specific antibody generated against this site, we found that α5-S16 phosphorylation is mitosis-specific in both yeast and mammalian cells. Blocking this site with a S16A mutation caused growth defect and G2/M arrest of the cell cycle. α5-S16 phosphorylation depends on CDK1 activity and is highly abundant in some but not all mitotic cells. Immunoprecipitation and mass spectrometry (IP-MS) studies identified numerous proteins that could interact with phosphorylated α5, including PLK1, a key regulator of mitosis. α5–PLK1 interaction increased upon mitosis and could be facilitated by S16 phosphorylation. CDK1 activation downstream of PLK1 activity was delayed in S16A mutant cells, suggesting an important role of α5-S16 phosphorylation in regulating PLK1 and mitosis. These data have revealed an unappreciated function of “exo-proteasome” phosphorylation of a proteasome subunit and may bring new insights to our understanding of cell cycle control.
format	article
author	Jinyuan Duan Wenzhu Li Xin Shu Bing Yang Xiangwei He Xing Guo
author_facet	Jinyuan Duan Wenzhu Li Xin Shu Bing Yang Xiangwei He Xing Guo
author_sort	Jinyuan Duan
title	Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
title_short	Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
title_full	Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
title_fullStr	Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
title_full_unstemmed	Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation
title_sort	conserved mitotic phosphorylation of a proteasome subunit regulates cell proliferation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9234c11d0216444abdc2783bed4d2794
work_keys_str_mv	AT jinyuanduan conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation AT wenzhuli conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation AT xinshu conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation AT bingyang conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation AT xiangweihe conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation AT xingguo conservedmitoticphosphorylationofaproteasomesubunitregulatescellproliferation
_version_	1718412665642024960

Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation

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