Perforin protein forms pores in the membrane to allow for granzyme B to enter the cell. Granzymes induce apoptosis by activating caspases. D4-GDP dissociation inhibitor (D4-GDI) is a negative regulator of ras-related Rho Family of GTPases. D4-GDI binds Rho GTPases to keep the Rho protein in a GDP-bound and inactivate state. Caspase 3 cleaves D4-GDI into two fragments of 5 kDa and 23 kDa size. The 23 kDa fragment translocates to the nucleus to activate Jun kinase, a regulator of apoptosis. Poly (ADP-ribose) polymerase-1 (PARP) is a substrate for caspase-3. Caspase-3 cleaves PARP into various fragments, this is a hallmark of apoptosis. PARP functions to detect and repair DNA damage. Cleavage of PARP by caspase prevents DNA repair, contributing to cell death. RHO GTPases become activated when released from D4-GDI upon cleavage by caspase-3. RHO GTPases mediate cytoskeleton changes leading to apoptosis and cell death. .

D4-GDI Signaling Pathway References