PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20
Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome and its co-activator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counter...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Cell Biology
2020
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| _version_ | 1797095615961759744 |
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| author | Bancroft, J Holder, J Geraghty, Z Alfonso-Pérez, T Murphy, D Barr, FA Gruneberg, U |
| author_facet | Bancroft, J Holder, J Geraghty, Z Alfonso-Pérez, T Murphy, D Barr, FA Gruneberg, U |
| author_sort | Bancroft, J |
| collection | OXFORD |
| description | Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome and its co-activator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Here, we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilises cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1-phosphorylation defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response, and rapidly destroy cyclin B once all chromosomes have aligned and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells. |
| first_indexed | 2024-03-07T04:30:25Z |
| format | Journal article |
| id | oxford-uuid:ce1ad674-e066-47dd-8cf3-e96705853a33 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:30:25Z |
| publishDate | 2020 |
| publisher | American Society for Cell Biology |
| record_format | dspace |
| spelling | oxford-uuid:ce1ad674-e066-47dd-8cf3-e96705853a332022-03-27T07:33:33ZPP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ce1ad674-e066-47dd-8cf3-e96705853a33EnglishSymplectic ElementsAmerican Society for Cell Biology2020Bancroft, JHolder, JGeraghty, ZAlfonso-Pérez, TMurphy, DBarr, FAGruneberg, UUbiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome and its co-activator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Here, we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilises cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1-phosphorylation defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response, and rapidly destroy cyclin B once all chromosomes have aligned and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells. |
| spellingShingle | Bancroft, J Holder, J Geraghty, Z Alfonso-Pérez, T Murphy, D Barr, FA Gruneberg, U PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title | PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title_full | PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title_fullStr | PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title_full_unstemmed | PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title_short | PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20 |
| title_sort | pp1 promotes cyclin b destruction and the metaphase anaphase transition by dephosphorylating cdc20 |
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