| Dismantling of the Components of the Nuclear Pore Comlex during Apoptosis | |
Abstract/OtherAbstract
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In HeLa 229 cells, exposure to TRAIL and etoposide resulted in characteristic apoptotic morphology, proteolytic activation of execution caspase-3 and-7 and oligonucleosomal DNA fragmentation. In the presence of the pan-caspase inhibitor z- VAD-fmk, apoptotic changes were inhibited. However, the rate of etoposide-induced apoptosis was much slower compared to receptor-mediated apoptosis. Cell synchronisation via the double thymidine block yielded a S-phase population of cells that underwent apoptosis upon DNA damage almost simultaneously and in a short time period and thereby enabled a more direct comparison between etoposide and TRAIL-induced apoptosis with regards to nuclear pore disassembly. Etoposide-induced apoptosis in synchronised HeLa cells was accompanied by chromatin condensation, proteolytic activation of execution caspase-3 and 7, oligonucleosomal DNA fragmentation, cytochrome c release and Bax translocation. Furthermore, these apoptotic endpoints were not influenced by the synchronisation procedure per se. A common set of nucleoporins which include the peripheral proteins Nup153, RanBP2, CAN/Nup214 and Nup50 and the sub-complex nuclear pore proteins Nup96 and Nup93 were cleaved in both TRAIL and etoposide-induced apoptosis. This proteolytic process occurred in a caspase-dependent manner, since z-VAD-fmk abolished cleavage of nucleoporins in both receptor-mediated and DNA damage mediated apoptosis. Furthermore, the cleavage of nuclear pore proteins was accompanied by the proteolysis of known caspase substrates namely Lamin B and PARP. However, PARP cleavage in the etoposide model appears to occur via a caspase independent mechanism. A number of common features regarding sequential degradation of the nuclear pore were observed in both apoptotic models. Nup93 and Nup96 were cleaved early, Tpr and Nup153 were cleaved concomitantly and CAN/Nup214 was cleaved late in both apoptotic models. When apoptosis was initiated at the plasma membrane, the order of cleavage was Nup93 and Nup96: Nup153, Tpr and RanBP2: NUP214 and Nup50. Apoptosis triggered at the nucleus resulted in the following sequence, Nup93, Nup96, Nup153, Tpr: RanBP2 and Nup50: NUP214. |
Authors
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Patre, Monika |
Contributors
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Publication Detail
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Publisher : Universität Konstanz, Fachbereich Biologie. Fachbereich Biologie Type : Thesis.Doctoral Format : application/pdf |
Date Detail
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2004 |
Subject
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Apoptosis, Caspasen, DNA-Schädigungen, Apoptose, Nuclear Pore, Apoptosis, Caspases, DNA damage, Etoposide, TRAIL, Life sciences |
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Relation
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Source
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Copyright Information
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http://kops.ub.uni-konstanz.de/doku/urheberrecht.php |
Other Details
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Languages : eng |
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