Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Cell Biol. 158 (6): 1051-1066

Copyright © 2002 by the Rockefeller University Press.


DEDD regulates degradation of intermediate filaments during apoptosis

Justine C. Lee1, Olaf Schickling1, Alexander H. Stegh1, Robert G. Oshima2, David Dinsdale3, Gerald M. Cohen3, and Marcus E. Peter1

1 The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637
2 The Burnham Institute, La Jolla, CA 92037
3 Medical Research Council Toxicology Unit, University of Leicester, Leicester LE1 9HN, United Kingdom

Address correspondence to Marcus Peter, The Ben May Institute for Cancer Research, University of Chicago, 924 E. 57th Street, Chicago, IL 60637. Tel.: (773) 702-4728. Fax: (773) 702-3701. E-mail: MPeter{at}

Abstract: Apoptosis depends critically on regulated cytoskeletal reorganization events in a cell. We demonstrate that death effector domain containing DNA binding protein (DEDD), a highly conserved and ubiquitous death effector domain containing protein, exists predominantly as mono- or diubiquitinated, and that diubiquitinated DEDD interacts with both the K8/18 intermediate filament network and pro–caspase-3. Early in apoptosis, both cytosolic DEDD and its close homologue DEDD2 formed filaments that colocalized with and depended on K8/18 and active caspase-3. Subsequently, these filamentous structures collapsed into intracellular inclusions that migrated into cytoplasmic blebs and contained DEDD, DEDD2, active caspase-3, and caspase-3–cleaved K18 late in apoptosis. Biochemical studies further confirmed that DEDD coimmunoprecipitated with both K18 and pro–caspase-3, and kinetic analyses placed apoptotic DEDD staining prior to caspase-3 activation and K18 cleavage. In addition, both caspase-3 activation and K18 cleavage was inhibited by expression of DEDD{Delta}NLS1-3, a cytosolic form of DEDD that cannot be ubiquitinated. Finally, siRNA mediated DEDD knockdown cells exhibited inhibition of staurosporine-induced DNA degradation. Our data suggest that DEDD represents a novel scaffold protein that directs the effector caspase-3 to certain substrates facilitating their ordered degradation during apoptosis.

Key Words: apoptosis; caspases; DEDD; intermediate filaments; monoubiquitination

Fibrils Colocalize Caspase-3 with Procaspase-3 to Foster Maturation.
J. A. Zorn, D. W. Wolan, N. J. Agard, and J. A. Wells (2012)
J. Biol. Chem. 287, 33781-33795
   Abstract »    Full Text »    PDF »
Biological Functions of Cytokeratin 18 in Cancer.
Y.-R. Weng, Y. Cui, and J.-Y. Fang (2012)
Mol. Cancer Res. 10, 485-493
   Abstract »    Full Text »    PDF »
Caspase-mediated apoptosis of trophoblasts in term human placental villi is restricted to cytotrophoblasts and absent from the multinucleated syncytiotrophoblast.
M. S. Longtine, B. Chen, A. O. Odibo, Y. Zhong, and D. M. Nelson (2012)
Reproduction 143, 107-121
   Abstract »    Full Text »    PDF »
Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required.
R. Kopp, T. Schwerte, M. Egg, A. M. Sandbichler, B. Egger, and B. Pelster (2010)
Physiol Genomics 42A, 8-23
   Abstract »    Full Text »    PDF »
Bre1p-mediated histone H2B ubiquitylation regulates apoptosis in Saccharomyces cerevisiae.
D. Walter, A. Matter, and B. Fahrenkrog (2010)
J. Cell Sci. 123, 1931-1939
   Abstract »    Full Text »    PDF »
Ubiquitin-Proteasome-mediated Degradation of Keratin Intermediate Filaments in Mechanically Stimulated A549 Cells.
A. Jaitovich, S. Mehta, N. Na, A. Ciechanover, R. D. Goldman, and K. M. Ridge (2008)
J. Biol. Chem. 283, 25348-25355
   Abstract »    Full Text »    PDF »
eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions.
Y.-M. Lin, Y.-R. Chen, J.-R. Lin, W.-J. Wang, A. Inoko, M. Inagaki, Y.-C. Wu, and R.-H. Chen (2008)
J. Cell Sci. 121, 2382-2393
   Abstract »    Full Text »    PDF »
Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm.
S. Kim and P. A. Coulombe (2007)
Genes & Dev. 21, 1581-1597
   Abstract »    Full Text »    PDF »
Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1.
S. Arai, K. Miyake, R. Voit, S. Nemoto, E. K. Wakeland, I. Grummt, and T. Miyazaki (2007)
PNAS 104, 2289-2294
   Abstract »    Full Text »    PDF »
Interaction between PCNA and Diubiquitinated Mcm10 Is Essential for Cell Growth in Budding Yeast.
S. Das-Bradoo, R. M. Ricke, and A.-K. Bielinsky (2006)
Mol. Cell. Biol. 26, 4806-4817
   Abstract »    Full Text »    PDF »
Assessment of Apoptosis by Immunohistochemical Markers Compared to Cellular Morphology in Ex Vivo-stressed Colonic Mucosa.
H. Holubec, C. M. Payne, H. Bernstein, K. Dvorakova, C. Bernstein, C. N. Waltmire, J. A. Warneke, and H. Garewal (2005)
Journal of Histochemistry & Cytochemistry 53, 229-235
   Abstract »    Full Text »    PDF »
Caspase Proteolysis of Desmin Produces a Dominant-negative Inhibitor of Intermediate Filaments and Promotes Apoptosis.
F. Chen, R. Chang, M. Trivedi, Y. Capetanaki, and V. L. Cryns (2003)
J. Biol. Chem. 278, 6848-6853
   Abstract »    Full Text »    PDF »
Efficient Reduction of Target RNAs by Small Interfering RNA and RNase H-dependent Antisense Agents. A COMPARATIVE ANALYSIS.
T. A. Vickers, S. Koo, C. F. Bennett, S. T. Crooke, N. M. Dean, and B. F. Baker (2003)
J. Biol. Chem. 278, 7108-7118
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882