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Molecular Oncology - 2023 - Quandt - CDK6 is activated by the atypical cyclin I to promote E2F‐mediated gene expression and.pdf (4.15 MB)

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2023-05-31

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cc by (c) Quandt, Eva et al, 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/201132

CDK6 is activated by the atypical cyclin I to promote <scp>E2F</scp>‐mediated gene expression and cancer cell proliferation

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Recurs relacionat

https://doi.org/10.1002/1878-0261.13438

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.

Matèries

Cicle cel·lular, Càncer de mama

Matèries (anglès)

Cell cycle, Breast cancer

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Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

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.. CDK6 is activated by the atypical cyclin I to promote <scp>E2F</scp>‐mediated gene expression and cancer cell proliferation. _Molecular Oncology_. 2023. Vol. 17, núm. 7, pàgs. 1228-1245. [consulta: 24 de gener de 2026]. ISSN: 1878-0261. [Disponible a: https://hdl.handle.net/2445/201132]

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