Changes in motility, gene expression and actin dynamics: Cdk6-induced cytoskeletal changes associated with...

Cyclin dependent kinase (cdk) 4 and cdk6 have historically been understood to be D-cyclin kinases that phosphorylate pRb in the nucleus to regulate G1 phase of the cell cycle. In conflict with this understood redundancy are several studies that have demonstrated a novel role for cdk6 in differentiation. Cdk6 expression must be reduced to allow proper osteoblast and osteoclast differentiation, enforced cdk6 expression blocked differentiation of mouse embryo fibroblasts, and cdk6 expression in primary astrocytes favored the expression of progenitor cell markers (Ericson et al. [2003] Mol Cancer Res 1:654-664; Matushansky et al. [2003] Oncogene 22:4143-4149; Ogasawara et al. [2004a] J Bone Miner Res 19:1128-1136; Ogasawara et al. [2004b] Mol Cell Biol 24:6560-6568). Experiments shown here investigate novel cytoplasmic and nuclear functions of cdk6. These data demonstrate that cdk6 expression in mouse astrocytes results in changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility. These changes in cdk6-infected cells are associated with the process of cellular differentiation.