A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis
Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics and chromosome orientation and is frequently found overexpressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO conjugating enzyme UBC9 and co-localizes with SUMO...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-12-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2011.00050/full |
| _version_ | 1818689244573466624 |
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| author | Ignacio ePérez de Castro Cristina eAguirre-Portolés Benedicte eMartin Gonzalo eFernández-Miranda Andrea eKlotzbucher Michael H. G. Kubbutat Diego eMegías Yannick eArlot-Bonnemains Marcos eMalumbres |
| author_facet | Ignacio ePérez de Castro Cristina eAguirre-Portolés Benedicte eMartin Gonzalo eFernández-Miranda Andrea eKlotzbucher Michael H. G. Kubbutat Diego eMegías Yannick eArlot-Bonnemains Marcos eMalumbres |
| author_sort | Ignacio ePérez de Castro |
| collection | DOAJ |
| description | Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics and chromosome orientation and is frequently found overexpressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO conjugating enzyme UBC9 and co-localizes with SUMO-1 in mitotic cells. Aurora-A can be SUMOylated in vitro and mutation in the highly conserved SUMOylation residue lysine 249 results in the induction of mitotic defects characterized by defective and multipolar spindles. The Aurora-AK249R mutant has normal kinase activity but it displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-AK249R mutant results in a significant increase in the susceptibility to malignant transformation induced by the Ras oncogene and an increased protection against apoptosis in tumor cells treated with mitotic poisons. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and suggest that deficient SUMOylation of this kinase may have relevant implications in tumor development or cancer therapy. |
| first_indexed | 2024-12-17T12:07:02Z |
| format | Article |
| id | doaj.art-1ec51dacb26f4028bf3982b14cc032c0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T12:07:02Z |
| publishDate | 2011-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1ec51dacb26f4028bf3982b14cc032c02022-12-21T21:49:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2011-12-01110.3389/fonc.2011.0005012483A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and OncogenesisIgnacio ePérez de Castro0Cristina eAguirre-Portolés1Benedicte eMartin2Gonzalo eFernández-Miranda3Andrea eKlotzbucher4Michael H. G. Kubbutat5Diego eMegías6Yannick eArlot-Bonnemains7Marcos eMalumbres8Centro Nacional de Investigaciones Oncológicas (CNIO)Centro Nacional de Investigaciones Oncológicas (CNIO)Université de RennesCentro Nacional de Investigaciones Oncológicas (CNIO)Proqinase GmBHProqinase GmBHCentro Nacional de Investigaciones Oncológicas (CNIO)Université de RennesCentro Nacional de Investigaciones Oncológicas (CNIO)Aurora-A is a serine/threonine kinase that plays critical roles in centrosome maturation, spindle dynamics and chromosome orientation and is frequently found overexpressed in human cancers. In this work, we show that Aurora-A interacts with the SUMO conjugating enzyme UBC9 and co-localizes with SUMO-1 in mitotic cells. Aurora-A can be SUMOylated in vitro and mutation in the highly conserved SUMOylation residue lysine 249 results in the induction of mitotic defects characterized by defective and multipolar spindles. The Aurora-AK249R mutant has normal kinase activity but it displays altered dynamics at the mitotic spindle. In addition, ectopic expression of the Aurora-AK249R mutant results in a significant increase in the susceptibility to malignant transformation induced by the Ras oncogene and an increased protection against apoptosis in tumor cells treated with mitotic poisons. These data suggest that modification by SUMO residues may control Aurora-A function at the spindle and suggest that deficient SUMOylation of this kinase may have relevant implications in tumor development or cancer therapy.http://journal.frontiersin.org/Journal/10.3389/fonc.2011.00050/fullMitosisSumoylationAurora kinasecancer targetmitotic spindle |
| spellingShingle | Ignacio ePérez de Castro Cristina eAguirre-Portolés Benedicte eMartin Gonzalo eFernández-Miranda Andrea eKlotzbucher Michael H. G. Kubbutat Diego eMegías Yannick eArlot-Bonnemains Marcos eMalumbres A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis Frontiers in Oncology Mitosis Sumoylation Aurora kinase cancer target mitotic spindle |
| title | A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis |
| title_full | A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis |
| title_fullStr | A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis |
| title_full_unstemmed | A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis |
| title_short | A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis |
| title_sort | sumoylation motif in aurora a implications in spindle dynamics and oncogenesis |
| topic | Mitosis Sumoylation Aurora kinase cancer target mitotic spindle |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2011.00050/full |
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