Reference - Detail
|Title||Changes in nuclear morphology during apoptosis correlate with vimentin cleavage by different caspases located either upstream or downstream of Bcl-2 action.|
BACKGROUND:Upon Fas stimulation, procaspase-8 is recruited to the death-inducing signalling complex where autoactivation of caspase-8 occurs. Active caspase-8 can directly activate downstream caspases (e.g. caspase-3, 6, and 7) for the execution of apoptosis (mitochondria-independent pathway), while caspase-8 can also lead to executioner caspase activation through mitochondrial damage (mitochondria-dependent pathway). Caspase activation results in the dismantling of intracellular structure through specific proteolysis.
RESULTS:We have found that an intermediate filament protein, vimentin, is cleaved at multiple sites by caspases at an early stage of apoptosis in Jurkat cells. The sequences of the two major cleavage sites in vimentin (IDVD/V and DSVD/F) suggested that these sites are cleaved by caspase-8 and caspase-3, respectively, or by close homologues of these proteases. The IDVD/V site can be cleaved by caspase-8 in vitro, and its cleavage is less sensitive to DEVD-CHO and Bcl-2 over-expression than that of the DSVD/F site in Jurkat cells. Over-expression of a mutant vimentin which was insensitive to caspase cleavage at these sites delayed the appearance of apoptotic nuclei in Jurkat cells.
CONCLUSION:The specific cleavage of vimentin can be used as an apoptotic marker of both apical- and mitochondria-dependent caspase activation. Apoptotic cleavage of vimentin most likely results in disruption of its filamentous structure, which may facilitate nuclear condensation and subsequent fragmentation through disruption of the cytoskeletal network.
|MeSH||Amino Acid Sequence Animals Apoptosis* / drug effects Calpain / antagonists & inhibitors Calpain / metabolism Caspase 3 Caspase 8 Caspase 9 Caspase Inhibitors Caspases / metabolism* Cell Nucleus / drug effects Cell Nucleus / metabolism* Cysteine Proteinase Inhibitors / pharmacology HeLa Cells Humans Jurkat Cells Lamins Mice Mutation Nuclear Proteins / metabolism Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism* Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Vimentin / chemistry Vimentin / genetics Vimentin / metabolism* fas Receptor / metabolism*|
|WOS Category||GENETICS & HEREDITY CELL BIOLOGY|
|Human and Animal Cells|