Inhibition of nuclear transport of caspase-7 by its prodomain.
Apoptosis is a major form of cell death, characterized by a series of morphological changes induced by cleaving cytoplasmic and nuclear proteins via active caspases. The data presented here show, by fluorescence microscopic and immunoblotting analyses, that a prodomain of caspase-7 inhibits its nuclear translocation and apoptosis-inducing activity. This nuclear localization is dependent on the presence of a basic tetrapeptide that is conserved in mammalian and Xenopus caspase-7 and that is located downstream of a cleavage site between a prodomain and a catalytic protease domain. Furthermore, an attachment of the caspase-7 prodomain (31 amino acids) represses the nuclear transport of a fusion protein of a heterologous protein and the caspase-7 nuclear localization signal (19 amino acids), suggesting that the inhibition of nuclear localization by the prodomain is mediated by the interaction of these short peptides.
Yaoita
Yoshio
Y
Division of Embryology and Genetics, Hiroshima University, Higashihiroshima, 739-8526, Japan. yaoita@hiroshima-u.ac.jp
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053179:Caspase 7; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017124:Conserved Sequence; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000235:genetics / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D053179:Caspase 7; D020169:Caspases