Caspases target only two architectural components within the core structure of the nuclear pore complex.
Caspases were recently implicated in the functional impairment of the nuclear pore complex during apoptosis, affecting its dual activity as nucleocytoplasmic transport channel and permeability barrier. Concurrently, electron microscopic data indicated that nuclear pore morphology is not overtly altered in apoptotic cells, raising the question of how caspases may deactivate nuclear pore function while leaving its overall structure largely intact. To clarify this issue we have analyzed the fate of all known nuclear pore proteins during apoptotic cell death. Our results show that only two of more than 20 nuclear pore core structure components, namely Nup93 and Nup96, are caspase targets. Both proteins are cleaved near their N terminus, disrupting the domains required for interaction with other nucleoporins actively involved in transport and providing the permeability barrier but dispensable for maintaining the nuclear pore scaffold. Caspase-mediated proteolysis of only few nuclear pore complex components may exemplify a general strategy of apoptotic cells to efficiently disable huge macromolecular machines.
Patre
Monika
M
Molecular Toxicology Group, Faculty of Biology, University of Konstanz, Germany.
Tabbert
Anja
A
Hermann
Daniela
D
Walczak
Henning
H
Rackwitz
Hans-Richard
HR
Cordes
Volker C
VC
Ferrando-May
Elisa
E
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008854:Microscopy, Electron; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry; D009707:Nucleosomes / Q000378:metabolism; D018272:Porins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016196:S Phase; D013997:Time Factors
C121702:NUP50 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C508154:Nup93 protein, human; D018272:Porins; C119239:nuclear pore complex protein 96; D005047:Etoposide; D004247:DNA; D020169:Caspases