CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation
Cyclin‐dependent kinases (CDKs), together with their cyclin partners, are the master cell cycle regulators. Remarkably, the cyclin family was extended to include atypical cyclins, characterized by distinctive structural features, but their partner CDKs remain elusive. Here, we conducted a yeast two‐...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-07-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13438 |
| _version_ | 1827906868996997120 |
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| author | Eva Quandt Núria Masip Sara Hernández‐Ortega Abril Sánchez‐Botet Laura Gasa Ainhoa Fernández‐Elorduy Sara Plutta Joan Marc Martínez‐Láinez Samuel Bru Pau M. Munoz‐Torres Martin Floor Jordi Villà‐Freixa May C. Morris August Vidal Alberto Villanueva Josep Clotet Mariana P. C. Ribeiro |
| author_facet | Eva Quandt Núria Masip Sara Hernández‐Ortega Abril Sánchez‐Botet Laura Gasa Ainhoa Fernández‐Elorduy Sara Plutta Joan Marc Martínez‐Láinez Samuel Bru Pau M. Munoz‐Torres Martin Floor Jordi Villà‐Freixa May C. Morris August Vidal Alberto Villanueva Josep Clotet Mariana P. C. Ribeiro |
| author_sort | Eva Quandt |
| collection | DOAJ |
| description | Cyclin‐dependent kinases (CDKs), together with their cyclin partners, are the master cell cycle regulators. Remarkably, the cyclin family was extended to include atypical cyclins, characterized by distinctive structural features, but their partner CDKs remain elusive. Here, we conducted a yeast two‐hybrid screen to identify new atypical cyclin–CDK complexes. We identified 10 new complexes, including a complex between CDK6 and cyclin I (CCNI), which was found to be active against retinoblastoma protein. CCNI upregulation increased the proliferation of breast cancer cells in vitro and in vivo, with a magnitude similar to that seen upon cyclin D upregulation, an effect that was abrogated by CDK6 silencing or palbociclib treatment. In line with these findings, CCNI downregulation led to a decrease in cell number and a reduction in the percentage of cells reaching S phase. Finally, CCNI upregulation correlated with the high expression of E2F target genes in large panels of cancer cell lines and tissue samples from breast cancer patients. In conclusion, we unveil CCNI as a new player in the pathways that activate CDK6, enriching the wiring of cell cycle control. |
| first_indexed | 2024-03-13T01:02:54Z |
| format | Article |
| id | doaj.art-4d91340f06a24d8eb0bf9f70674462b3 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-13T01:02:54Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-4d91340f06a24d8eb0bf9f70674462b32023-07-06T09:54:22ZengWileyMolecular Oncology1574-78911878-02612023-07-011771228124510.1002/1878-0261.13438CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferationEva Quandt0Núria Masip1Sara Hernández‐Ortega2Abril Sánchez‐Botet3Laura Gasa4Ainhoa Fernández‐Elorduy5Sara Plutta6Joan Marc Martínez‐Láinez7Samuel Bru8Pau M. Munoz‐Torres9Martin Floor10Jordi Villà‐Freixa11May C. Morris12August Vidal13Alberto Villanueva14Josep Clotet15Mariana P. C. Ribeiro16Basic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainDepartment of Biosciences, Faculty of Sciences, Technology and Engineering Universitat de Vic – Universitat Central de Catalunya SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainInstitut des Biomolécules Max Mousseron, CNRS‐UMR5247 Université de Montpellier FranceServei d'Anatomia Patològica Hospital Universitari de Bellvitge Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainBasic Science Department, Faculty of Medicine and Health Sciences Universitat Internacional de Catalunya Barcelona SpainCyclin‐dependent kinases (CDKs), together with their cyclin partners, are the master cell cycle regulators. Remarkably, the cyclin family was extended to include atypical cyclins, characterized by distinctive structural features, but their partner CDKs remain elusive. Here, we conducted a yeast two‐hybrid screen to identify new atypical cyclin–CDK complexes. We identified 10 new complexes, including a complex between CDK6 and cyclin I (CCNI), which was found to be active against retinoblastoma protein. CCNI upregulation increased the proliferation of breast cancer cells in vitro and in vivo, with a magnitude similar to that seen upon cyclin D upregulation, an effect that was abrogated by CDK6 silencing or palbociclib treatment. In line with these findings, CCNI downregulation led to a decrease in cell number and a reduction in the percentage of cells reaching S phase. Finally, CCNI upregulation correlated with the high expression of E2F target genes in large panels of cancer cell lines and tissue samples from breast cancer patients. In conclusion, we unveil CCNI as a new player in the pathways that activate CDK6, enriching the wiring of cell cycle control.https://doi.org/10.1002/1878-0261.13438atypical cyclinsCDK6E2Fpalbociclibretinoblastoma |
| spellingShingle | Eva Quandt Núria Masip Sara Hernández‐Ortega Abril Sánchez‐Botet Laura Gasa Ainhoa Fernández‐Elorduy Sara Plutta Joan Marc Martínez‐Láinez Samuel Bru Pau M. Munoz‐Torres Martin Floor Jordi Villà‐Freixa May C. Morris August Vidal Alberto Villanueva Josep Clotet Mariana P. C. Ribeiro CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation Molecular Oncology atypical cyclins CDK6 E2F palbociclib retinoblastoma |
| title | CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation |
| title_full | CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation |
| title_fullStr | CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation |
| title_full_unstemmed | CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation |
| title_short | CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and cancer cell proliferation |
| title_sort | cdk6 is activated by the atypical cyclin i to promote e2f mediated gene expression and cancer cell proliferation |
| topic | atypical cyclins CDK6 E2F palbociclib retinoblastoma |
| url | https://doi.org/10.1002/1878-0261.13438 |
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