Role for cyclin-dependent kinase 2 in mitosis exit.
Mitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from mitosis depends on the inactivation of the complex by the degradation of cyclin B [2]. Cdk2 is also active during mitosis [3, 4]. In Xenopus egg extracts, cdk2 is primarily in complex with cyclin E, which is stable [5]...
| Główni autorzy: | , , , , , |
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| Format: | Journal article |
| Język: | English |
| Wydane: |
2001
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| _version_ | 1826297385863610368 |
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| author | D'Angiolella, V Costanzo, V Gottesman, M Avvedimento, E Gautier, J Grieco, D |
| author_facet | D'Angiolella, V Costanzo, V Gottesman, M Avvedimento, E Gautier, J Grieco, D |
| author_sort | D'Angiolella, V |
| collection | OXFORD |
| description | Mitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from mitosis depends on the inactivation of the complex by the degradation of cyclin B [2]. Cdk2 is also active during mitosis [3, 4]. In Xenopus egg extracts, cdk2 is primarily in complex with cyclin E, which is stable [5]. At the end of mitosis, downregulation of cdk2-cyclin E activity is accompanied by inhibitory phosphorylation of cdk2 [6]. Here, we show that cdk2-cyclin E activity maintains cdk1-cyclin B during mitosis. At mitosis exit, cdk2 is inactivated prior to cdk1. The loss of cdk2 activity follows and depends upon an increase in protein kinase A (PKA) activity. Prematurely inactivating cdk2 advances the time of cyclin B degradation and cdk1 inactivation. Blocking PKA, instead, stabilizes cdk2 activity and inhibits cyclin B degradation and cdk1 inactivation. The stabilization of cdk1-cyclin B is also induced by a mutant cdk2-cyclin E complex that is resistant to inhibitory phosphorylation. P21-Cip1, which inhibits both wild-type and mutant cdk2-cyclin E, reverses mitotic arrest under either condition. Our findings indicate that the proteolysis-independent downregulation of cdk2 activity at the end of mitosis depends on PKA and is required to activate the proteolysis cascade that leads to mitosis exit. |
| first_indexed | 2024-03-07T04:30:48Z |
| format | Journal article |
| id | oxford-uuid:ce3f2168-b72d-4446-82f6-3db0ec0c3c0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:30:48Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:ce3f2168-b72d-4446-82f6-3db0ec0c3c0c2022-03-27T07:34:23ZRole for cyclin-dependent kinase 2 in mitosis exit.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ce3f2168-b72d-4446-82f6-3db0ec0c3c0cEnglishSymplectic Elements at Oxford2001D'Angiolella, VCostanzo, VGottesman, MAvvedimento, EGautier, JGrieco, DMitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from mitosis depends on the inactivation of the complex by the degradation of cyclin B [2]. Cdk2 is also active during mitosis [3, 4]. In Xenopus egg extracts, cdk2 is primarily in complex with cyclin E, which is stable [5]. At the end of mitosis, downregulation of cdk2-cyclin E activity is accompanied by inhibitory phosphorylation of cdk2 [6]. Here, we show that cdk2-cyclin E activity maintains cdk1-cyclin B during mitosis. At mitosis exit, cdk2 is inactivated prior to cdk1. The loss of cdk2 activity follows and depends upon an increase in protein kinase A (PKA) activity. Prematurely inactivating cdk2 advances the time of cyclin B degradation and cdk1 inactivation. Blocking PKA, instead, stabilizes cdk2 activity and inhibits cyclin B degradation and cdk1 inactivation. The stabilization of cdk1-cyclin B is also induced by a mutant cdk2-cyclin E complex that is resistant to inhibitory phosphorylation. P21-Cip1, which inhibits both wild-type and mutant cdk2-cyclin E, reverses mitotic arrest under either condition. Our findings indicate that the proteolysis-independent downregulation of cdk2 activity at the end of mitosis depends on PKA and is required to activate the proteolysis cascade that leads to mitosis exit. |
| spellingShingle | D'Angiolella, V Costanzo, V Gottesman, M Avvedimento, E Gautier, J Grieco, D Role for cyclin-dependent kinase 2 in mitosis exit. |
| title | Role for cyclin-dependent kinase 2 in mitosis exit. |
| title_full | Role for cyclin-dependent kinase 2 in mitosis exit. |
| title_fullStr | Role for cyclin-dependent kinase 2 in mitosis exit. |
| title_full_unstemmed | Role for cyclin-dependent kinase 2 in mitosis exit. |
| title_short | Role for cyclin-dependent kinase 2 in mitosis exit. |
| title_sort | role for cyclin dependent kinase 2 in mitosis exit |
| work_keys_str_mv | AT dangiolellav roleforcyclindependentkinase2inmitosisexit AT costanzov roleforcyclindependentkinase2inmitosisexit AT gottesmanm roleforcyclindependentkinase2inmitosisexit AT avvedimentoe roleforcyclindependentkinase2inmitosisexit AT gautierj roleforcyclindependentkinase2inmitosisexit AT griecod roleforcyclindependentkinase2inmitosisexit |