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Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity
The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonst...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255618/ https://www.ncbi.nlm.nih.gov/pubmed/34235154 http://dx.doi.org/10.3389/fcell.2021.692269 |
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author | Wang, Faliang Zhu, Cuige Cai, Shirong Boudreau, Aaron Kim, Sun-Joong Bissell, Mina Shao, Jieya |
author_facet | Wang, Faliang Zhu, Cuige Cai, Shirong Boudreau, Aaron Kim, Sun-Joong Bissell, Mina Shao, Jieya |
author_sort | Wang, Faliang |
collection | PubMed |
description | The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonstrated that both nuclear localization and PLP-binding are required for tumor growth inhibition by Pfn1, and this is at least partially due to Pfn1 association with the PLP-containing ENL protein in the Super Elongation Complex (SEC) and the transcriptional inhibition of pro-cancer genes. In this paper, by identifying a phosphorylation event of Pfn1 at Ser(71) capable of inhibiting its actin-binding and nuclear export, we provide in vitro and in vivo evidence that chemotherapy-induced apoptotic sensitization by Pfn1 requires its cytoplasmic localization and actin-binding. With regard to tumor growth inhibition byPfn1, our data indicate a requirement for dynamic actin association and dissociation rendered by reversible Ser(71)phosphorylation and dephosphorylation. Furthermore, genetic and pharmacological experiments showed that Ser(71) of Pfn1 can be phosphorylated by protein kinase A (PKA). Taken together, our data provide novel mechanistic insights into the multifaceted anticancer activities of Pfn1 and how they are spatially-defined in the cell and differentially regulated by ligand-binding. |
format | Online Article Text |
id | pubmed-8255618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82556182021-07-06 Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity Wang, Faliang Zhu, Cuige Cai, Shirong Boudreau, Aaron Kim, Sun-Joong Bissell, Mina Shao, Jieya Front Cell Dev Biol Cell and Developmental Biology The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonstrated that both nuclear localization and PLP-binding are required for tumor growth inhibition by Pfn1, and this is at least partially due to Pfn1 association with the PLP-containing ENL protein in the Super Elongation Complex (SEC) and the transcriptional inhibition of pro-cancer genes. In this paper, by identifying a phosphorylation event of Pfn1 at Ser(71) capable of inhibiting its actin-binding and nuclear export, we provide in vitro and in vivo evidence that chemotherapy-induced apoptotic sensitization by Pfn1 requires its cytoplasmic localization and actin-binding. With regard to tumor growth inhibition byPfn1, our data indicate a requirement for dynamic actin association and dissociation rendered by reversible Ser(71)phosphorylation and dephosphorylation. Furthermore, genetic and pharmacological experiments showed that Ser(71) of Pfn1 can be phosphorylated by protein kinase A (PKA). Taken together, our data provide novel mechanistic insights into the multifaceted anticancer activities of Pfn1 and how they are spatially-defined in the cell and differentially regulated by ligand-binding. Frontiers Media S.A. 2021-06-21 /pmc/articles/PMC8255618/ /pubmed/34235154 http://dx.doi.org/10.3389/fcell.2021.692269 Text en Copyright © 2021 Wang, Zhu, Cai, Boudreau, Kim, Bissell and Shao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Wang, Faliang Zhu, Cuige Cai, Shirong Boudreau, Aaron Kim, Sun-Joong Bissell, Mina Shao, Jieya Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title | Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title_full | Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title_fullStr | Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title_full_unstemmed | Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title_short | Ser(71) Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity |
title_sort | ser(71) phosphorylation inhibits actin-binding of profilin-1 and its apoptosis-sensitizing activity |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255618/ https://www.ncbi.nlm.nih.gov/pubmed/34235154 http://dx.doi.org/10.3389/fcell.2021.692269 |
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