Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage.
A number of lines of evidence have suggested a possible involvement of the mitosis-promoting protein kinase Cdc2 in the process of apoptotic cell death, and one recent study concluded that premature activation of Cdc2 is required for apoptosis. Here we have used a temperature-sensitive murine Cdc2 m...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1995
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| _version_ | 1826285900823265280 |
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| author | Ongkeko, W Ferguson, D Harris, A Norbury, C |
| author_facet | Ongkeko, W Ferguson, D Harris, A Norbury, C |
| author_sort | Ongkeko, W |
| collection | OXFORD |
| description | A number of lines of evidence have suggested a possible involvement of the mitosis-promoting protein kinase Cdc2 in the process of apoptotic cell death, and one recent study concluded that premature activation of Cdc2 is required for apoptosis. Here we have used a temperature-sensitive murine Cdc2 mutant cell line and Cdc2 inhibitor compounds to study the effect of inhibition of this protein kinase on apoptosis induced by DNA-damaging drugs. Inhibition of Cdc2 activity before or during exposure to DNA strand break-inducing drugs had the effect of increasing the level of subsequent apoptosis, as assessed by electron microscopy and flow cytometry. We conclude that, far from being required for cell death, a form of mammalian Cdc2 suppresses apoptosis induced by DNA damage. This form of Cdc2 appears to be active in G2-arrested cells and is therefore presumably distinct from the mitosis-promoting Cdc2-cyclin B heterodimer. |
| first_indexed | 2024-03-07T01:35:46Z |
| format | Journal article |
| id | oxford-uuid:9522089e-54d6-41f8-a6f6-5d7a0a4dbe20 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:35:46Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:9522089e-54d6-41f8-a6f6-5d7a0a4dbe202022-03-26T23:44:05ZInactivation of Cdc2 increases the level of apoptosis induced by DNA damage.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9522089e-54d6-41f8-a6f6-5d7a0a4dbe20EnglishSymplectic Elements at Oxford1995Ongkeko, WFerguson, DHarris, ANorbury, CA number of lines of evidence have suggested a possible involvement of the mitosis-promoting protein kinase Cdc2 in the process of apoptotic cell death, and one recent study concluded that premature activation of Cdc2 is required for apoptosis. Here we have used a temperature-sensitive murine Cdc2 mutant cell line and Cdc2 inhibitor compounds to study the effect of inhibition of this protein kinase on apoptosis induced by DNA-damaging drugs. Inhibition of Cdc2 activity before or during exposure to DNA strand break-inducing drugs had the effect of increasing the level of subsequent apoptosis, as assessed by electron microscopy and flow cytometry. We conclude that, far from being required for cell death, a form of mammalian Cdc2 suppresses apoptosis induced by DNA damage. This form of Cdc2 appears to be active in G2-arrested cells and is therefore presumably distinct from the mitosis-promoting Cdc2-cyclin B heterodimer. |
| spellingShingle | Ongkeko, W Ferguson, D Harris, A Norbury, C Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title | Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title_full | Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title_fullStr | Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title_full_unstemmed | Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title_short | Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. |
| title_sort | inactivation of cdc2 increases the level of apoptosis induced by dna damage |
| work_keys_str_mv | AT ongkekow inactivationofcdc2increasesthelevelofapoptosisinducedbydnadamage AT fergusond inactivationofcdc2increasesthelevelofapoptosisinducedbydnadamage AT harrisa inactivationofcdc2increasesthelevelofapoptosisinducedbydnadamage AT norburyc inactivationofcdc2increasesthelevelofapoptosisinducedbydnadamage |