CDK6 is activated by the atypical cyclin I to promote <scp>E2F</scp>‐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-...

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Detalles Bibliográficos
Autores: Quandt, Eva, Masip, Núria, Hernández Ortega, Sara, Sánchez Botet, Abril, Gasa, Laura, Fernández Elorduy, Ainhoa, Plutta, Sara, Martínez Láinez, Joan Marc, Bru, Samuel, Muñoz Torres, Pau M., Floor, Martin, Villà Freixa, Jordi, Morris, May C., Vidal, August, Villanueva Garatachea, Alberto, Clotet Erra, Josep, Ribeiro, Mariana P. C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/201132
Acceso en línea:https://hdl.handle.net/2445/201132
Access Level:acceso abierto
Palabra clave:Cicle cel·lular
Càncer de mama
Cell cycle
Breast cancer
Descripción
Sumario: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.

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