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Sci. STKE, 24 September 2002
Vol. 2002, Issue 151, p. tw346
[DOI: 10.1126/stke.2002.151.tw346]


Apoptosis Cytoskeletal Death Scaffold

The protein known as death effector domain-containing DNA binding protein (DEDD) has a number of unusual properties. It is an abundant protein and is evolutionarily conserved. It has three nuclear localization signals and, as the name suggests, binds to DNA and chromatin, yet it is often found in the cytoplasm. Lee et al. propose a function of the DEDD in the cytoplasm as a scaffold that localizes caspase-3 to the intermediate filament network. Induction of apoptosis in HeLa cells caused aggregation of DEDD in filamentous structures in a manner that depended on activity of caspase-3. These structures contain cytokeratins 8 and 18, components of the intermediate filament network. Immunofluorescence microscopy with an antibody specific for active caspase-3 also showed colocalization of DEDD with the active caspase. Immmunoprecipitation studies showed association of DEDD with caspase-3 and cytokeratin 18. Expression of a dominant-negative form of DEDD or reduced expression of DEDD caused by a small interfering RNA inhibited activation of caspase-3 in response to apoptotic stimuli. The authors note that there are some 40,000 putative caspase-3 cleavage sites in the approximately 34,000 known protein sequences. They propose that specificity for substrate cleavage may require specific targeting of caspases to their substrates through protein-protein interactions with scaffolding proteins like DEDD.

J. C. Lee, O. Schickling, A. H. Stegh, R. G. Oshima, D. Dinsdale, G. M. Cohen, M. E. Peter, DEDD regulates degradation of intermediate filaments during apoptosis. J. Cell Biol. 158, 1051-1066 (2002). [Abstract] [Full Text]

Citation: Cytoskeletal Death Scaffold. Sci. STKE 2002, tw346 (2002).

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