Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP

Abstract The PBAF chromatin-remodeling complexes are multi-protein machines, regulating expression of genes involved in proliferation and differentiation. PHF10 is a subunit of the PBAF essential for its association with chromatin. Mammalian PHF10 is expressed as four ubiquitous isoforms, which are...

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Autores principales:	Victor V. Tatarskiy, Yuriy P. Simonov, Dmitrii S. Shcherbinin, Alexander V. Brechalov, Sofia G. Georgieva, Nataliya V. Soshnikova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/59ced0be4ab848c393157bf2ba51b36b
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spelling	oai:doaj.org-article:59ced0be4ab848c393157bf2ba51b36b2021-12-02T15:05:13ZStability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP10.1038/s41598-017-05944-32045-2322https://doaj.org/article/59ced0be4ab848c393157bf2ba51b36b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05944-3https://doaj.org/toc/2045-2322Abstract The PBAF chromatin-remodeling complexes are multi-protein machines, regulating expression of genes involved in proliferation and differentiation. PHF10 is a subunit of the PBAF essential for its association with chromatin. Mammalian PHF10 is expressed as four ubiquitous isoforms, which are alternatively incorporated in the complex and differ by their influence on transcription of target genes. PHF10 have different domain structure and two of them (PHF10-S isoforms) lack C-terminal PHD domains, which enables their phosphorylation by CK-1. Here we have found that PBAF subunits have low turnover rate, except for PHF10 which has much lower half-life, and is degraded by β-TrCP. The β-TrCP knockdown stabilizes PBAF core subunits - BRG1 and BAF155 and specific subunits - PHF10, BAF200, BAF180 and BRD7. PHF10 isoforms contain two non-canonical β-TrCP degrons and are degraded by β-TrCP in a phospho-dependent manner. But phosphorylation of PHF10-S degrons by CK-1, contrary to previously described degrons, prevents their degradation. Targeted molecular docking demonstrated that phosphorylated forms of PHF10 bind to β-TrCP with much lower affinity than non-phosphorylated ones, contrary to previously described degrons. This unorthodox mechanism proposes that phosphorylation of β-TrCP degrons by CK-1 could not only degrade a set of proteins, but also stabilize a different set of targets.Victor V. TatarskiyYuriy P. SimonovDmitrii S. ShcherbininAlexander V. BrechalovSofia G. GeorgievaNataliya V. SoshnikovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victor V. Tatarskiy Yuriy P. Simonov Dmitrii S. Shcherbinin Alexander V. Brechalov Sofia G. Georgieva Nataliya V. Soshnikova Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
description	Abstract The PBAF chromatin-remodeling complexes are multi-protein machines, regulating expression of genes involved in proliferation and differentiation. PHF10 is a subunit of the PBAF essential for its association with chromatin. Mammalian PHF10 is expressed as four ubiquitous isoforms, which are alternatively incorporated in the complex and differ by their influence on transcription of target genes. PHF10 have different domain structure and two of them (PHF10-S isoforms) lack C-terminal PHD domains, which enables their phosphorylation by CK-1. Here we have found that PBAF subunits have low turnover rate, except for PHF10 which has much lower half-life, and is degraded by β-TrCP. The β-TrCP knockdown stabilizes PBAF core subunits - BRG1 and BAF155 and specific subunits - PHF10, BAF200, BAF180 and BRD7. PHF10 isoforms contain two non-canonical β-TrCP degrons and are degraded by β-TrCP in a phospho-dependent manner. But phosphorylation of PHF10-S degrons by CK-1, contrary to previously described degrons, prevents their degradation. Targeted molecular docking demonstrated that phosphorylated forms of PHF10 bind to β-TrCP with much lower affinity than non-phosphorylated ones, contrary to previously described degrons. This unorthodox mechanism proposes that phosphorylation of β-TrCP degrons by CK-1 could not only degrade a set of proteins, but also stabilize a different set of targets.
format	article
author	Victor V. Tatarskiy Yuriy P. Simonov Dmitrii S. Shcherbinin Alexander V. Brechalov Sofia G. Georgieva Nataliya V. Soshnikova
author_facet	Victor V. Tatarskiy Yuriy P. Simonov Dmitrii S. Shcherbinin Alexander V. Brechalov Sofia G. Georgieva Nataliya V. Soshnikova
author_sort	Victor V. Tatarskiy
title	Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
title_short	Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
title_full	Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
title_fullStr	Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
title_full_unstemmed	Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP
title_sort	stability of the phf10 subunit of pbaf signature module is regulated by phosphorylation: role of β-trcp
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/59ced0be4ab848c393157bf2ba51b36b
work_keys_str_mv	AT victorvtatarskiy stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp AT yuriypsimonov stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp AT dmitriisshcherbinin stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp AT alexandervbrechalov stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp AT sofiaggeorgieva stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp AT nataliyavsoshnikova stabilityofthephf10subunitofpbafsignaturemoduleisregulatedbyphosphorylationroleofbtrcp
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Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP

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