Prothymosin alpha fragmentation in apoptosis

We observed fragmentation of an essential proliferation-related human nucle ar protein prothymosin alpha in the course of apoptosis induced by various stimuli, Prothymosin alpha cleavage occurred at the DDVD99 motif. In vitro, prothymosin alpha could be cleaved at D-99 by caspase-3 and -7. Caspase hy drolysis disrupted the nuclear localization signal of prothymosin alpha and abrogated the ability of the truncated protein to accumulate inside the nu cleus. Prothymosin alpha fragmentation may therefore be proposed to disable intranuclear proliferation-related function of prothymosin alpha in two wa ys: by cleaving off a short peptide containing important determinants, and by preventing active nuclear uptake of the truncated protein. (C) 2000 Fede ration of European Biochemical Societies.