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 apoptosis by cleaving several key cellular proteins. Despite their function in apoptosis, little is known about where in the cell they are localized and whether they are translocated to specific cellular compartments upon activation. In the present paper, using Aequorea victoria green fluorescent protein fusion constructs, we have determined the localization of Nedd2 (mouse caspase-2) and show that both precursor and processed caspase-2 localize to the cytoplasmic and the nuclear compartments. We demonstrate that the nuclear localization of caspase-2 is strictly dependent on the presence of the prodomain. A caspase-2 prodomain-green fluorescent protein localized to dot- and fiber-like structures mostly in the nucleus, whereas a protein lacking the prodomain was largely concentrated in the cytoplasm. We also show that an amino-terminal fusion of the prodomain of caspase-2 to caspase-3 mediates nuclear transport of caspase-3, which is normally localized in the cytoplasm. These results suggest that, in addition to roles in dimerization and recruitment through adaptors, the caspase-2 prodomain has a novel function in nuclear transport.
Colussi
P A
PA
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia.
Harvey
N L
NL
Kumar
S
S
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D053143:Caspase 2; D020169:Caspases; D002467:Cell Nucleus / Q000201:enzymology*; D003546:Cysteine Endopeptidases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology; D017931:DNA Primers; D004792:Enzyme Precursors / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D037401:Scyphozoa; D014162:Transfection
D017931:DNA Primers; D004792:Enzyme Precursors; D008164:Luminescent Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D053143:Caspase 2; D020169:Caspases; D003546:Cysteine Endopeptidases