D4-GDI (GDP dissociation inhibitor) is a negative regulator of the ras-related Rho family of GTPases. Since the Rho GTPases promote cytoskeletal and membrane changes associated with apoptotic cell death, the removal of the D4-GDI block through its cleavage is important for inducing apoptosis. Caspase-3 cleaves the 28kD mature form of D4-GDI to give a 23kD and 5kD size fragment. The 23kD fragment then translocates to the nucleus. The mechanisms involving cleavage of D4-GDI with apoptosis are not presently known. Activation of the Jun N-terminal kinase, a regulator of apoptosis, may be one of the mechanisms.