Abstract
Rho guanine nucleotide dissociation inhibitors (RhoGDIs) regulate the activity of Rho family GTPases. RhoGDIβ (LyGDI/GDID4/RhoGDI2) has two caspase cleavage sites after Asp19 and Asp55. The resulting cleavage products, ΔN(1-19)RhoGDIβ and ΔN(1-55)RhoGDIβ, are expressed in cells under conditions that activate caspases. ΔN(1-19)RhoGDIβ, which can inhibit GDP dissociation, is implicated in the process of apoptosis, and ΔN(1-55)RhoGDIβ, which lacks the ability to inhibit GDP dissociation, is implicated in the process of anoikis, a form of apoptosis which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix. Here, we found a novel cleavage site of RhoGDIβ in X-irradiated BALB/c 3T3 1-1src cells. This site, which contains the consensus sequence for cleavage by downstream caspases, is likely to be cleaved by an unknown caspase other than caspases-1, -3, -7, -8, and -9 because neither caspases are activated in the irradiated 1-1src cells. Diverse forms of cleaved RhoGDIβ represent a guaranteed system for cell death generated by intracellular signaling network.
