CDK6 is activated by the atypical cyclin I to promote E2F-mediated gene expression and cancer cell proliferation
Author
Quandt, Eva
Masip, Núria
Hernández-Ortega, Sara
Sánchez-Botet, Abril
Gasa, Laura
Fernández-Elorduy, Ainhoa
Plutta, Sara
Martínez-Láinez, Joan Marc
Bru, Samuel
Munoz-Torres, Pau M.
Floor, Martin
Villà-Freixa, Jordi
Morris, May C.
Vidal, August
Villanueva, Alberto
Clotet, Josep
Ribeiro, Mariana P. C.
Publication date
2023ISSN
1878-0261
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Ciclina atípica
CDK6
E2F
Palbociclib
Retinoblastoma
Ciclina atípica
CDK6
E2F
Palbociclib
Retinoblastoma
Atypical cyclin
CDK6
E2F
Palbociclib
Retinoblastoma
Pages
18
Publisher
John Wiley & Sons
Is part of
Molecular Oncology
Citation
Quandt, Eva; Masip, 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, p.1-18. Disponible en: <https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13438>. Fecha de acceso: 21 jun. 2023. DOI: 10.1002/1878-0261.13438
Link to the related item
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- Ciències de la Salut [568]
Rights
Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/