Caspases disrupt the nuclear-cytoplasmic barrier.
During apoptosis, caspases, a family of proteases, disassemble a cell by cleaving a set of proteins. Caspase-3 plays a major role in the dissassembly of the nucleus by processing several nuclear substrates. The question is how caspase-3 which is usually cytoplasmic, gains access to its nuclear targets. It was suggested that caspase-3 is actively transported to the nucleus through the nuclear pores. We found that caspase-9, which is activated earlier than caspase-3, directly or indirectly inactivates nuclear transport and increases the diffusion limit of the nuclear pores. This increase allows caspase-3 and other molecules that could not pass through the nuclear pores in living cells to enter or leave the nucleus during apoptosis by diffusion. Hence, caspase-9 contributes to cell disassembly by disrupting the nuclear cytoplasmic barrier.
Faleiro
L
L
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA.
Lazebnik
Y
Y
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology*; D004058:Diffusion; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D022022:Nuclear Pore / Q000201:enzymology*; D013049:Spectrin / Q000737:chemistry / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology
D000970:Antineoplastic Agents; D009419:Nerve Tissue Proteins; C417303:betaIV spectrin; D013049:Spectrin; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D002945:Cisplatin