REGULATION OF CYTOSKELETAL FUNCTIONS BY RHO-SMALL GTP-BINDING PROTEINS IN NORMAL AND CANCER-CELLS

The actin cytoskeleton is involved in numerous cellular functions such as cell motility, mitogenesis, morphology, muscle contraction, cytoki nesis, and establishment of cell polarity. The members of the Rho subf amily of small GTP-binding proteins emerge as key regulators of cytosk eleton organization. Rho, Rac, and CDC42 are implicated in the regulat ion of actin microfilament organization of different cell structures, such as stress fibers linked to focal adhesions and membrane ruffles i nduced by extracellular stimuli. Rho proteins also regulate the activi ty of several enzymes involved in the formation of phospholipid deriva tives, which could mediate their effect on the cytoskeleton. The activ ity of Rho proteins is regulated by many nucleotide exchange factors a nd GTPase-activating proteins, some of which are oncogene products, an d other disease-associated proteins. The potential role of these small GTP-binding proteins in carcinogenesis is suggested by the actin reor ganization seen in transforming cells and by the need for functional R ho proteins in Ras mitogenic activation.