Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Morgan, M. Articles by Thorburn, A. Search for Related Content PubMed PubMed Citation Articles by Morgan, M. Articles by Thorburn, A. Social Bookmarking                      What's this?

¹ Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157
² Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

Address correspondence to Andrew Thorburn, Wake Forest University School of Medicine, Department of Cancer Biology, Medical Center Boulevard, Winston-Salem, NC 27157. Tel.: (336) 716-7587. Fax: (336) 715-0255. E-mail: athorbur{at}wfubmc.edu

The adapter protein tumor necrosis factor receptor (TNFR)1–associated death domain (TRADD) plays an essential role in recruiting signaling molecules to the TNFRI receptor complex at the cell membrane. Here we show that TRADD contains a nuclear export and import sequence that allow shuttling between the nucleus and the cytoplasm. In the absence of export, TRADD is found within nuclear structures that are associated with promyelocytic leukemia protein (PML) nuclear bodies. In these structures, the TRADD death domain (TRADD-DD) can activate an apoptosis pathway that is mechanistically distinct from its action at the membrane-bound TNFR1 complex. Apoptosis by nuclear TRADD-DD is promyelocytic leukemia protein dependent, involves p53, and is inhibited by Bcl-xL but not by caspase inhibitors or dominant negative FADD (FADD-DN). Conversely, apoptosis induced by TRADD in the cytoplasm is resistant to Bcl-xL, but sensitive to caspase inhibitors and FADD-DN. These data indicate that nucleocytoplasmic shuttling of TRADD leads to the activation of distinct apoptosis mechanisms that connect the death receptor apparatus to nuclear events.

Key Words: apoptosis; TRADD; leptomycin B; PML; p53

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Chen, J., Cheng, X., Merched-Sauvage, M., Caulin, C., Roop, D. R., Koch, P. J. (2006). An unexpected role for keratin 10 end domains in susceptibility to skin cancer. J. Cell Sci. 119: 5067-5076 [Abstract] [Full Text]  
• Shiio, Y., Rose, D. W., Aur, R., Donohoe, S., Aebersold, R., Eisenman, R. N. (2006). Identification and Characterization of SAP25, a Novel Component of the mSin3 Corepressor Complex. Mol. Cell. Biol. 26: 1386-1397 [Abstract] [Full Text]  
• Nakagawa, M., Hosokawa, Y., Yonezumi, M., Izumiyama, K., Suzuki, R., Tsuzuki, S., Asaka, M., Seto, M. (2005). MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Blood 106: 4210-4216 [Abstract] [Full Text]  
• Poon, I. K.H., Oro, C., Dias, M. M., Zhang, J., Jans, D. A. (2005). Apoptin Nuclear Accumulation Is Modulated by a CRM1-Recognized Nuclear Export Signal that Is Active in Normal but not in Tumor Cells. Cancer Res. 65: 7059-7064 [Abstract] [Full Text]  
• Yang, Y., Ma, J., Chen, Y., Wu, M. (2004). Nucleocytoplasmic Shuttling of Receptor-interacting Protein 3 (RIP3): IDENTIFICATION OF NOVEL NUCLEAR EXPORT AND IMPORT SIGNALS IN RIP3. J. Biol. Chem. 279: 38820-38829 [Abstract] [Full Text]  
• Chau, B. N., Chen, T.-T., Wan, Y. Y., DeGregori, J., Wang, J. Y. J. (2004). Tumor Necrosis Factor Alpha-Induced Apoptosis Requires p73 and c-ABL Activation Downstream of RB Degradation. Mol. Cell. Biol. 24: 4438-4447 [Abstract] [Full Text]  
• Py, B., Slomianny, C., Auberger, P., Petit, P. X., Benichou, S. (2004). Siva-1 and an Alternative Splice Form Lacking the Death Domain, Siva-2, Similarly Induce Apoptosis in T Lymphocytes via a Caspase-Dependent Mitochondrial Pathway. J. Immunol. 172: 4008-4017 [Abstract] [Full Text]  
• Giraud, S., Diaz-Latoud, C., Hacot, S., Textoris, J., Bourette, R. P., Diaz, J.-J. (2004). US11 of Herpes Simplex Virus Type 1 Interacts with HIPK2 and Antagonizes HIPK2-Induced Cell Growth Arrest. J. Virol. 78: 2984-2993 [Abstract] [Full Text]  
• Fotin-Mleczek, M., Henkler, F., Hausser, A., Glauner, H., Samel, D., Graness, A., Scheurich, P., Mauri, D., Wajant, H. (2004). Tumor Necrosis Factor Receptor-associated Factor (TRAF) 1 Regulates CD40-induced TRAF2-mediated NF-{kappa}B Activation. J. Biol. Chem. 279: 677-685 [Abstract] [Full Text]  
• Henkler, F., Baumann, B., Fotin-Mleczek, M., Weingartner, M., Schwenzer, R., Peters, N., Graness, A., Wirth, T., Scheurich, P., Schmid, J. A., Wajant, H. (2003). Caspase-mediated Cleavage Converts the Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-1 from a Selective Modulator of TNF Receptor Signaling to a General Inhibitor of NF-{kappa}B Activation. J. Biol. Chem. 278: 29216-29230 [Abstract] [Full Text]  
• Yazidi-Belkoura, I. E., Adriaenssens, E., Dolle, L., Descamps, S., Hondermarck, H. (2003). Tumor Necrosis Factor Receptor-associated Death Domain Protein Is Involved in the Neurotrophin Receptor-mediated Antiapoptotic Activity of Nerve Growth Factor in Breast Cancer Cells. J. Biol. Chem. 278: 16952-16956 [Abstract] [Full Text]  
• Screaton, R. A., Kiessling, S., Sansom, O. J., Millar, C. B., Maddison, K., Bird, A., Clarke, A. R., Frisch, S. M. (2003). Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: A potential link between genome surveillance and apoptosis. Proc. Natl. Acad. Sci. USA 100: 5211-5216 [Abstract] [Full Text]  
• Watters, C. (2002). Video Views and Reviews. cellbioed 1: 111-114 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents