CDK6 is activated by the atypical cyclin I to promote E2F-mediated gene expression and cancer cell proliferation
Visualitza/Obre
Autor/a
Sánchez‑Botet, Abril
Gasa, Laura
Munoz-Torres, Pau M.
Villanueva, Alberto
Data de publicació
2023ISSN
1878-0261
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
61 - Medicina
616.3 - Patologia de l'aparell digestiu. Odontologia
Paraules clau
Càncer
Cáncer
Cancer
Pàgines
17
Publicat per
Wiley
Col·lecció
17; 7
Publicat a
Molecular Oncology
Citació
Quandt Herrera, Eva; Masip Sales, Núria; Hernández Ortega, Sara [et al.]. CDK6 is activated by the atypical cyclin I to promote E2F-mediated gene expression and cancer cell proliferation. Molecular Oncology, 2023, 17, p. 1228-1245. Disponible en: <https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13438>. Fecha de acceso: 21 may. 2024. DOI: 10.1002/1878-0261.13438
Aquest element apareix en la col·lecció o col·leccions següent(s)
- Ciències de la Salut [740]
Drets
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