PRODOMAIN-DEPENDENT NUCLEAR-LOCALIZATION OF THE CASPASE-2 (NEDD2) PRECURSOR - A NOVEL FUNCTION FOR A CASPASE PRODOMAIN

Caspases are cysteine proteases that play an essential role in apoptos is by cleaving several key cellular proteins. Despite their function i n apoptosis, little is known about where in the cell they are localize d and whether they are translocated to specific cellular compartments upon activation. In the present paper, using Aequorea victoria green f luorescent protein fusion constructs, we have determined the localizat ion of Nedd2 (mouse caspase-2) and show that both precursor and proces sed caspase-2 localize to the cytoplasmic and the nuclear compartments . We demonstrate that the nuclear localization of caspase-2 is strictl y dependent on the presence of the prodomain. A caspase-2 prodomain-gr een fluorescent protein localized to dot- and fiber-like structures mo stly in the nucleus, whereas a protein lacking the prodomain was large ly concentrated in the cytoplasm, We also show that an amino-terminal fusion of the prodomain of caspase-2 to caspase-3 mediates nuclear tra nsport of caspase-3, which is normally localized in the cytoplasm. The se results suggest that, in addition to roles in dimerization and recr uitment through adaptors, the caspase-2 prodomain has a novel function in nuclear transport.