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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.

Cancer: Proteins that work together could reveal drug targets Studying the activity of proteins that work together to control cell division is revealing several that might be suitable targets for new drugs to fight cancer. Researchers led by Josep Clotet and Mariana Ribeiro at the International University of Catalonia, Barcelona, Spain, investigated the activities of the complex formed between two proteins, CDK16 and CCNY. CDK16 is an enzyme that modifies other molecules by adding phosphate groups (PO4) to them. CCNY is a protein that controls the activity of CDK16 and other proteins. Previous research has suggested a role for the complex in the development of cancer, but the mechanism has been unclear. The researchers found that the CDK16/CCNY complex activates proteins that control the network of microtubules in cells known as the cytoskeleton. One of these proteins, PRC1, is essential for cell division.