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.
Subscribe

Logo for

J. Biol. Chem. 275 (49): 38905-38911

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Essential Role for Caspase-8 in Transcription-independent Apoptosis Triggered by p53*

Han-Fei DingDagger §, Yi-Ling LinDagger , Gaël McGillDagger , Peter Juo||, Hong Zhu||, John Blenis||, Junying Yuan||, and David E. FisherDagger **

From the Dagger  Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, Massachusetts 02115 and || Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

p53's dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and -independent mechanisms. It is shown here that caspase-8 is activated early in cells undergoing p53-mediated apoptosis and in S100 cell-free extracts that recapitulate transcription-independent apoptosis. Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wild-type p53. Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway.

* This work was supported in part by Grant CA69531from the National Institutes of Health (to D.E.F.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by the Howard Temin Award from NCI, National Institutes of Health, and a Special Fellowship from the Leukemia and Lymphoma Society.

Recipient of a Howard Hughes Medical Institute predoctoral fellowship.

** Nirenberg Fellow at the Dana-Farber Cancer Institute. To whom correspondence should be addressed: D630, Division of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Children's Hospital, 44 Binney St., Boston, MA 02115. Tel.: 617-632-4916; Fax: 617-632-2085; E-mail: david_fisher@dfci.harvard.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Identification of a Novel Cell Death Receptor Mediating IGFBP-3-induced Anti-tumor Effects in Breast and Prostate Cancer.
A. R. Ingermann, Y.-F. Yang, J. Han, A. Mikami, A. E. Garza, L. Mohanraj, L. Fan, M. Idowu, J. L. Ware, H.-S. Kim, et al. (2010)
J. Biol. Chem. 285, 30233-30246
   Abstract »    Full Text »    PDF »
Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.
K. Liu, S. Zhou, J.-Y. Kim, K. Tillison, D. Majors, D. Rearick, J. H. Lee, R. F. Fernandez-Boyanapalli, K. Barricklow, M. S. Houston, et al. (2009)
Am J Physiol Endocrinol Metab 297, E1395-E1413
   Abstract »    Full Text »    PDF »
p53 Acetylation Is Crucial for Its Transcription-independent Proapoptotic Functions.
H. Yamaguchi, N. T. Woods, L. G. Piluso, H.-H. Lee, J. Chen, K. N. Bhalla, A. Monteiro, X. Liu, M.-C. Hung, and H.-G. Wang (2009)
J. Biol. Chem. 284, 11171-11183
   Abstract »    Full Text »    PDF »
Simultaneous exposure to dietary acrylamide and corn oil developed carcinogenesis through cell proliferation and inhibition of apoptosis by regulating p53-mediated mitochondria-dependent signaling pathway.
X Zhang (2009)
Toxicology and Industrial Health 25, 101-109
   Abstract »    PDF »
Oligomerization of BAK by p53 Utilizes Conserved Residues of the p53 DNA Binding Domain.
E. C. Pietsch, E. Perchiniak, A. A. Canutescu, G. Wang, R. L. Dunbrack, and M. E. Murphy (2008)
J. Biol. Chem. 283, 21294-21304
   Abstract »    Full Text »    PDF »
Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death.
J. Y. Kim, K. Liu, S. Zhou, K. Tillison, Y. Wu, and C. M. Smas (2008)
Am J Physiol Endocrinol Metab 294, E654-E667
   Abstract »    Full Text »    PDF »
Oxygen regulation of arterial smooth muscle cell proliferation and survival.
J. B. Ray, S. Arab, Y. Deng, P. Liu, L. Penn, D. W. Courtman, and M. E. Ward (2008)
Am J Physiol Heart Circ Physiol 294, H839-H852
   Abstract »    Full Text »    PDF »
Adaptor Protein LAPF Recruits Phosphorylated p53 to Lysosomes and Triggers Lysosomal Destabilization in Apoptosis.
N. Li, Y. Zheng, W. Chen, C. Wang, X. Liu, W. He, H. Xu, and X. Cao (2007)
Cancer Res. 67, 11176-11185
   Abstract »    Full Text »    PDF »
Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands.
N. Ishimaru, R. Arakaki, F. Omotehara, K. Yamada, K. Mishima, I. Saito, and Y. Hayashi (2006)
Mol. Cell. Biol. 26, 2924-2935
   Abstract »    Full Text »    PDF »
Caspase-8 Can Be Activated by Interchain Proteolysis without Receptor-triggered Dimerization during Drug-induced Apoptosis.
D. Sohn, K. Schulze-Osthoff, and R. U. Janicke (2005)
J. Biol. Chem. 280, 5267-5273
   Abstract »    Full Text »    PDF »
p53 Activation Domain 1 Is Essential for PUMA Upregulation and p53-Mediated Neuronal Cell Death.
S. P. Cregan, N. A. Arbour, J. G. MacLaurin, S. M. Callaghan, A. Fortin, E. C. C. Cheung, D. S. Guberman, D. S. Park, and R. S. Slack (2004)
J. Neurosci. 24, 10003-10012
   Abstract »    Full Text »    PDF »
Dietary Corn Oil Promotes Colon Cancer by Inhibiting Mitochondria-Dependent Apoptosis in Azoxymethane-Treated Rats.
B. Wu, R. Iwakiri, A. Ootani, S. Tsunada, T. Fujise, Y. Sakata, H. Sakata, S. Toda, and K. Fujimoto (2004)
Exp Biol Med 229, 1017-1025
   Abstract »    Full Text »    PDF »
Regulation of Bax Activation and Apoptotic Response to Microtubule-damaging Agents by p53 Transcription-dependent and -independent Pathways.
H. Yamaguchi, J. Chen, K. Bhalla, and H.-G. Wang (2004)
J. Biol. Chem. 279, 39431-39437
   Abstract »    Full Text »    PDF »
Transcriptional repression by p53 promotes a Bcl-2-insensitive and mitochondria-independent pathway of apoptosis.
N. Godefroy, S. Bouleau, G. Gruel, F. Renaud, V. Rincheval, B. Mignotte, D. Tronik-Le Roux, and J.-L. Vayssiere (2004)
Nucleic Acids Res. 32, 4480-4490
   Abstract »    Full Text »    PDF »
In Vivo Mitochondrial p53 Translocation Triggers a Rapid First Wave of Cell Death in Response to DNA Damage That Can Precede p53 Target Gene Activation.
S. Erster, M. Mihara, R. H. Kim, O. Petrenko, and U. M. Moll (2004)
Mol. Cell. Biol. 24, 6728-6741
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor Alpha-Induced Apoptosis Requires p73 and c-ABL Activation Downstream of RB Degradation.
B. N. Chau, T.-T. Chen, Y. Y. Wan, J. DeGregori, and J. Y. J. Wang (2004)
Mol. Cell. Biol. 24, 4438-4447
   Abstract »    Full Text »    PDF »
Intratumor Administration of Interleukin 13 Receptor-targeted Cytotoxin Induces Apoptotic Cell Death in Human Malignant Glioma Tumor Xenografts.
M. Kawakami, K. Kawakami, and R. K. Puri (2002)
Mol. Cancer Ther. 1, 999-1007
   Abstract »    Full Text »    PDF »
Active Caspase-8 Translocates into the Nucleus of Apoptotic Cells to Inactivate Poly(ADP-ribose) Polymerase-2.
A. Benchoua, C. Couriaud, C. Guegan, L. Tartier, P. Couvert, G. Friocourt, J. Chelly, J. Menissier-de Murcia, and B. Onteniente (2002)
J. Biol. Chem. 277, 34217-34222
   Abstract »    Full Text »    PDF »
p53 Mediates DNA Damaging Drug-induced Apoptosis through a Caspase-9-dependent Pathway in SH-SY5Y Neuroblastoma Cells.
H. Cui, A. Schroering, and H.-F. Ding (2002)
Mol. Cancer Ther. 1, 679-686
   Abstract »    Full Text »    PDF »
Transcription Profile of Cells Infected with Human T-cell Leukemia Virus Type I Compared with Activated Lymphocytes.
C. A. Pise-Masison, M. Radonovich, R. Mahieux, P. Chatterjee, C. Whiteford, J. Duvall, C. Guillerm, A. Gessain, and J. N. Brady (2002)
Cancer Res. 62, 3562-3571
   Abstract »    Full Text »    PDF »
Lipopolysaccharide-Induced Apoptosis of Endothelial Cells and Its Inhibition by Vascular Endothelial Growth Factor.
N. Munshi, A. Z. Fernandis, R. P. Cherla, I.-W. Park, and R. K. Ganju (2002)
J. Immunol. 168, 5860-5866
   Abstract »    Full Text »    PDF »
Loss of p53 Compensates for alpha v-Integrin Function in Retinal Neovascularization.
S. Stromblad, A. Fotedar, H. Brickner, C. Theesfeld, E. Aguilar de Diaz, M. Friedlander, and D. A. Cheresh (2002)
J. Biol. Chem. 277, 13371-13374
   Abstract »    Full Text »    PDF »
Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins.
D. G. Stupack, X. S. Puente, S. Boutsaboualoy, C. M. Storgard, and D. A. Cheresh (2001)
J. Cell Biol. 155, 459-470
   Abstract »    Full Text »    PDF »
B Cell Receptor Cross-Linking Triggers a Caspase-8- Dependent Apoptotic Pathway That Is Independent of the Death Effector Domain of Fas-Associated Death Domain Protein.
L. Besnault, N. Schrantz, M. T. Auffredou, G. Leca, M. F. Bourgeade, and A. Vazquez (2001)
J. Immunol. 167, 733-740
   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