SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression
Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remai...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713003938 |
| _version_ | 1811277212423290880 |
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| author | Hidefumi Fukushima Kohei Ogura Lixin Wan Ying Lu Victor Li Daming Gao Pengda Liu Alan W. Lau Tao Wu Marc W. Kirschner Hiroyuki Inuzuka Wenyi Wei |
| author_facet | Hidefumi Fukushima Kohei Ogura Lixin Wan Ying Lu Victor Li Daming Gao Pengda Liu Alan W. Lau Tao Wu Marc W. Kirschner Hiroyuki Inuzuka Wenyi Wei |
| author_sort | Hidefumi Fukushima |
| collection | DOAJ |
| description | Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCFβ-TRCP reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCFβ-TRCP. Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions. |
| first_indexed | 2024-04-13T00:12:46Z |
| format | Article |
| id | doaj.art-93eff70712a54ef1bd6806af0f7b0a38 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T00:12:46Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-93eff70712a54ef1bd6806af0f7b0a382022-12-22T03:11:03ZengElsevierCell Reports2211-12472013-08-014480381610.1016/j.celrep.2013.07.031SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle ProgressionHidefumi Fukushima0Kohei Ogura1Lixin Wan2Ying Lu3Victor Li4Daming Gao5Pengda Liu6Alan W. Lau7Tao Wu8Marc W. Kirschner9Hiroyuki Inuzuka10Wenyi Wei11Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAProper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCFβ-TRCP reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCFβ-TRCP. Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions.http://www.sciencedirect.com/science/article/pii/S2211124713003938 |
| spellingShingle | Hidefumi Fukushima Kohei Ogura Lixin Wan Ying Lu Victor Li Daming Gao Pengda Liu Alan W. Lau Tao Wu Marc W. Kirschner Hiroyuki Inuzuka Wenyi Wei SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression Cell Reports |
| title | SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression |
| title_full | SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression |
| title_fullStr | SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression |
| title_full_unstemmed | SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression |
| title_short | SCF-Mediated Cdh1 Degradation Defines a Negative Feedback System that Coordinates Cell-Cycle Progression |
| title_sort | scf mediated cdh1 degradation defines a negative feedback system that coordinates cell cycle progression |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713003938 |
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