The extracellular-regulated protein kinase 5 (ERK5) promotes cell proliferation through the down-regulation of inhibitors of cyclin dependent protein kinases (CDKs)

► ERK5 is critical for G1 to S phase transition of the cell cycle. ► Increased CKI expression caused by the loss of ERK5 results in reduced CDK2 activity. ► ERK5, but not ERK1/2, is required to suppress p21 expression in primary fibroblasts. ► Inhibition of ERK5 prevents breast cancer cells to proliferate. ► ERK5-mediated up-regulation of miRNAs reduces p21 level in breast cancer cells.