Cargando…
A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1
To enter into mitosis, cells must shut off the cell cycle inhibitor Wee1. SAD family protein kinases regulate Wee1 signaling in yeast and humans. In Schizosaccharomyces pombe, two SAD kinases (Cdr1/Nim1 and Cdr2) act as upstream inhibitors of Wee1. Previous studies found that S. pombe Cdr1/Nim1 dire...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880885/ https://www.ncbi.nlm.nih.gov/pubmed/31644361 http://dx.doi.org/10.1091/mbc.E19-08-0430 |
_version_ | 1783473842773032960 |
---|---|
author | Opalko, Hannah E. Nasa, Isha Kettenbach, Arminja N. Moseley, James B. |
author_facet | Opalko, Hannah E. Nasa, Isha Kettenbach, Arminja N. Moseley, James B. |
author_sort | Opalko, Hannah E. |
collection | PubMed |
description | To enter into mitosis, cells must shut off the cell cycle inhibitor Wee1. SAD family protein kinases regulate Wee1 signaling in yeast and humans. In Schizosaccharomyces pombe, two SAD kinases (Cdr1/Nim1 and Cdr2) act as upstream inhibitors of Wee1. Previous studies found that S. pombe Cdr1/Nim1 directly phosphorylates and inhibits Wee1 in vitro, but different results were obtained for budding yeast and human SAD kinases. Without a full understanding of Cdr1 action on Wee1, it has been difficult to assess the in vivo relevance and conservation of this mechanism. Here, we show that both Cdr1 and Cdr2 promote Wee1 phosphorylation in cells, but only Cdr1 inhibits Wee1 kinase activity. Inhibition occurs when Cdr1 phosphorylates a cluster of serine residues linking α-helices G and H of the Wee1 kinase domain. This region is highly divergent among different Wee1 proteins, consistent with distinct regulatory mechanisms. A wee(4A) mutant that impairs phosphorylation by Cdr1 delays mitotic entry and causes elongated cells. By disrupting and retargeting Cdr1 localization, we show that Cdr1 inhibition of Wee1 occurs in cells at cortical nodes formed by Cdr2. On the basis of our results, we propose a two-step model for inhibition of Wee1 by Cdr1 and Cdr2 at nodes. |
format | Online Article Text |
id | pubmed-6880885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-68808852020-02-16 A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 Opalko, Hannah E. Nasa, Isha Kettenbach, Arminja N. Moseley, James B. Mol Biol Cell Brief Report To enter into mitosis, cells must shut off the cell cycle inhibitor Wee1. SAD family protein kinases regulate Wee1 signaling in yeast and humans. In Schizosaccharomyces pombe, two SAD kinases (Cdr1/Nim1 and Cdr2) act as upstream inhibitors of Wee1. Previous studies found that S. pombe Cdr1/Nim1 directly phosphorylates and inhibits Wee1 in vitro, but different results were obtained for budding yeast and human SAD kinases. Without a full understanding of Cdr1 action on Wee1, it has been difficult to assess the in vivo relevance and conservation of this mechanism. Here, we show that both Cdr1 and Cdr2 promote Wee1 phosphorylation in cells, but only Cdr1 inhibits Wee1 kinase activity. Inhibition occurs when Cdr1 phosphorylates a cluster of serine residues linking α-helices G and H of the Wee1 kinase domain. This region is highly divergent among different Wee1 proteins, consistent with distinct regulatory mechanisms. A wee(4A) mutant that impairs phosphorylation by Cdr1 delays mitotic entry and causes elongated cells. By disrupting and retargeting Cdr1 localization, we show that Cdr1 inhibition of Wee1 occurs in cells at cortical nodes formed by Cdr2. On the basis of our results, we propose a two-step model for inhibition of Wee1 by Cdr1 and Cdr2 at nodes. The American Society for Cell Biology 2019-12-01 /pmc/articles/PMC6880885/ /pubmed/31644361 http://dx.doi.org/10.1091/mbc.E19-08-0430 Text en © 2019 Opalko et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Brief Report Opalko, Hannah E. Nasa, Isha Kettenbach, Arminja N. Moseley, James B. A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title | A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title_full | A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title_fullStr | A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title_full_unstemmed | A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title_short | A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry by inhibiting Wee1 |
title_sort | mechanism for how cdr1/nim1 kinase promotes mitotic entry by inhibiting wee1 |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880885/ https://www.ncbi.nlm.nih.gov/pubmed/31644361 http://dx.doi.org/10.1091/mbc.E19-08-0430 |
work_keys_str_mv | AT opalkohannahe amechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT nasaisha amechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT kettenbacharminjan amechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT moseleyjamesb amechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT opalkohannahe mechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT nasaisha mechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT kettenbacharminjan mechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 AT moseleyjamesb mechanismforhowcdr1nim1kinasepromotesmitoticentrybyinhibitingwee1 |