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The study identified new atypical cyclin-CDK complexes through a yeast two-hybrid screen, including a complex between CDK6 and cyclin I (CCNI). CCNI was found to be active against retinoblastoma protein and upregulation increased the proliferation of breast cancer cells both in vitro and in vivo, similar to the effect of cyclin D upregulation. CDK6 silencing or palbociclib treatment abrogated this effect. CCNI downregulation led to a decrease in cell number and a reduction in the percentage of cells reaching S-phase. CCNI upregulation also correlated with high expression of E2F target genes in large panels of cancer cell lines and tissue samples from breast cancer patients. This discovery adds CCNI as a new player in the pathways that activate CDK6, enriching the understanding of cell cycle control.
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