PROTEOLYSIS OF FODRIN (NONERYTHROID SPECTRIN) DURING APOPTOSIS

Several recent studies have implicated proteases as important triggers of apoptosis. Thus far, substrates that are cleaved during apoptosis have been elusive. In this report we demonstrate that cleavage of alph a-fodrin (non erythroid spectrin) accompanies apoptosis, induced by ac tivation via the CD3/T cell receptor complex in a murine T cell hybrid oma, ligation of the Fas (CD95) molecule on a human T cell lymphoma li ne and other Fas-expressing cells, or treatment of cells with staurosp orine, dexamethasone, or synthetic ceramide. Furthermore, inhibition o f activation-induced apoptosis by pretreatment of T hybridoma cells wi th antisense oligonucleotides directed against c-myc also inhibited fo drin proteolysis, confirming that this cleavage process is tightly cou pled to apoptosis. Fodrin cleavage during ap optosis may have implicat ions for the membrane blebbing seen during this process.