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Rapid calcium-dependent activation of Aurora-A kinase
Oncogenic hyperactivation of the mitotic kinase Aurora-A (AurA) in cancer is associated with genomic instability. Increasing evidence indicates that AurA also regulates critical processes in normal interphase cells, but the source of such activity has been obscure. We report here that multiple stimu...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963827/ https://www.ncbi.nlm.nih.gov/pubmed/20842194 http://dx.doi.org/10.1038/ncomms1061 |
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author | Plotnikova, Olga V. Pugacheva, Elena N. Dunbrack, Roland L. Golemis, Erica A. |
author_facet | Plotnikova, Olga V. Pugacheva, Elena N. Dunbrack, Roland L. Golemis, Erica A. |
author_sort | Plotnikova, Olga V. |
collection | PubMed |
description | Oncogenic hyperactivation of the mitotic kinase Aurora-A (AurA) in cancer is associated with genomic instability. Increasing evidence indicates that AurA also regulates critical processes in normal interphase cells, but the source of such activity has been obscure. We report here that multiple stimuli causing release of Ca(2+) from intracellular endoplasmic reticulum stores rapidly and transiently activate AurA, without requirement for second messengers. This activation is mediated by direct Ca(2+)-dependent calmodulin (CaM) binding to multiple motifs on AurA. On the basis of structure–function analysis and molecular modelling, we map two primary regions of CaM-AurA interaction to unfolded sequences in the AurA N- and C-termini. This unexpected mechanism for AurA activation provides a new context for evaluating the function of AurA and its inhibitors in normal and cancerous cells. |
format | Text |
id | pubmed-2963827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-29638272010-11-05 Rapid calcium-dependent activation of Aurora-A kinase Plotnikova, Olga V. Pugacheva, Elena N. Dunbrack, Roland L. Golemis, Erica A. Nat Commun Article Oncogenic hyperactivation of the mitotic kinase Aurora-A (AurA) in cancer is associated with genomic instability. Increasing evidence indicates that AurA also regulates critical processes in normal interphase cells, but the source of such activity has been obscure. We report here that multiple stimuli causing release of Ca(2+) from intracellular endoplasmic reticulum stores rapidly and transiently activate AurA, without requirement for second messengers. This activation is mediated by direct Ca(2+)-dependent calmodulin (CaM) binding to multiple motifs on AurA. On the basis of structure–function analysis and molecular modelling, we map two primary regions of CaM-AurA interaction to unfolded sequences in the AurA N- and C-termini. This unexpected mechanism for AurA activation provides a new context for evaluating the function of AurA and its inhibitors in normal and cancerous cells. Nature Publishing Group 2010-09 /pmc/articles/PMC2963827/ /pubmed/20842194 http://dx.doi.org/10.1038/ncomms1061 Text en Copyright © 2010, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Plotnikova, Olga V. Pugacheva, Elena N. Dunbrack, Roland L. Golemis, Erica A. Rapid calcium-dependent activation of Aurora-A kinase |
title | Rapid calcium-dependent activation of Aurora-A kinase |
title_full | Rapid calcium-dependent activation of Aurora-A kinase |
title_fullStr | Rapid calcium-dependent activation of Aurora-A kinase |
title_full_unstemmed | Rapid calcium-dependent activation of Aurora-A kinase |
title_short | Rapid calcium-dependent activation of Aurora-A kinase |
title_sort | rapid calcium-dependent activation of aurora-a kinase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963827/ https://www.ncbi.nlm.nih.gov/pubmed/20842194 http://dx.doi.org/10.1038/ncomms1061 |
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