MUTATIONAL ANALYSIS OF HUMAN PROTHYMOSIN-ALPHA REVEALS A BIPARTITE NUCLEAR-LOCALIZATION SIGNAL

Mutants of human prothymosin alpha with impaired ability to inhibit ye ast Saccharomyces cerevisiae. cerevisiae cell growth were characterize d, Two types of prothymosin alpha-inactivating mutations were observed , Mutations that belong to the first type compromised the nuclear entr y of prothymosin alpha by affecting its nuclear localization signal. A nalysis of subcellular distribution of GFP-prothymosin alpha fusions r evealed a bipartite nuclear localization signal that is both necessary and sufficient for nuclear import of the protein in human cells, Muta tions of the second type abrogated the inhibitory action of prothymosi n alpha through an unknown mechanism, without influencing the nuclear import of the protein. (C) 1997 Federation of European Biochemical Soc ieties.