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

This Article Full Text Full Text (PDF, 965K) PPT slides of all figures 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 JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Golks, A. Articles by Lavrik, I. N. Search for Related Content PubMed PubMed Citation Articles by Golks, A. Articles by Lavrik, I. N. Social Bookmarking                      What's this?

The c-FLIP–NH₂ terminus (p22-FLIP) induces NF-B activation

Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany

CORRESPONDENCE Peter H. Krammer: p.krammer{at}dkfz.de

c-FLIP proteins (isoforms: c-FLIP_L, c-FLIP_S, and c-FLIP_R) play an essential role in the regulation of death receptor–induced apoptosis. Here, we demonstrate that the cytoplasmic NH₂-terminal procaspase-8 cleavage product of c-FLIP (p22-FLIP) found in nonapoptotic malignant cells, primary T and B cells, and mature dendritic cells (DCs) strongly induces nuclear factor B (NF-B) activity by interacting with the IB kinase (IKK) complex via the IKK subunit. Thus, in addition to inhibiting apoptosis by binding to the death-inducing signaling complex, our data demonstrate a novel mechanism by which c-FLIP controls NF-B activation and life/death decisions in lymphocytes and DCs.

Abbreviations used: CHX, cycloheximide; DED, death effector domain; DISC, death-inducing signaling complex; EMSA, electrophoretic mobility shift assay; IKK, IB kinase complex; siRNA, small interfering RNA.

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

This article has been cited by other articles:

• Yu, J. W., Jeffrey, P. D., Shi, Y. (2009). Mechanism of procaspase-8 activation by c-FLIPL. Proc. Natl. Acad. Sci. USA 106: 8169-8174 [Abstract] [Full Text]  
• Klemke, C.-D., Brenner, D., Weiss, E.-M., Schmidt, M., Leverkus, M., Gulow, K., Krammer, P. H. (2009). Lack of T-Cell Receptor-Induced Signaling Is Crucial for CD95 Ligand Up-regulation and Protects Cutaneous T-Cell Lymphoma Cells from Activation-Induced Cell Death. Cancer Res. 69: 4175-4183 [Abstract] [Full Text]  
• Nichols, D. B., Shisler, J. L. (2009). Poxvirus MC160 Protein Utilizes Multiple Mechanisms To Inhibit NF-{kappa}B Activation Mediated via Components of the Tumor Necrosis Factor Receptor 1 Signal Transduction Pathway. J. Virol. 83: 3162-3174 [Abstract] [Full Text]  
• Kiessling, M. K., Klemke, C. D., Kaminski, M. M., Galani, I. E., Krammer, P. H., Gulow, K. (2009). Inhibition of Constitutively Activated Nuclear Factor-{kappa}B Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma. Cancer Res. 69: 2365-2374 [Abstract] [Full Text]  
• Caprioli, F, Stolfi, C, Caruso, R, Fina, D, Sica, G, Biancone, L, Pallone, F, Monteleone, G (2008). Transcriptional and post-translational regulation of Flip, an inhibitor of Fas-mediated apoptosis, in human gut inflammation. Gut 57: 1674-1680 [Abstract] [Full Text]  
• Ferrarini, M., Delfanti, F., Gianolini, M., Rizzi, C., Alfano, M., Lazzarin, A., Biswas, P. (2008). NF-{kappa}B Modulates Sensitivity to Apoptosis, Proinflammatory and Migratory Potential in Short- versus Long-Term Cultured Human {gamma}{delta} Lymphocytes. J. Immunol. 181: 5857-5864 [Abstract] [Full Text]  
• Ueffing, N., Schuster, M., Keil, E., Schulze-Osthoff, K., Schmitz, I. (2008). Up-regulation of c-FLIPshort by NFAT contributes to apoptosis resistance of short-term activated T cells. Blood 112: 690-698 [Abstract] [Full Text]  
• Zhang, N., Hopkins, K., He, Y.-W. (2008). The Long Isoform of Cellular FLIP Is Essential for T Lymphocyte Proliferation through an NF-{kappa}B-Independent Pathway. J. Immunol. 180: 5506-5511 [Abstract] [Full Text]  
• Suvannasankha, A., Crean, C. D., Shanmugam, R., Farag, S. S., Abonour, R., Boswell, H. S., Nakshatri, H. (2008). Antimyeloma Effects of a Sesquiterpene Lactone Parthenolide. Clin. Cancer Res. 14: 1814-1822 [Abstract] [Full Text]  
• Wang, L., Azad, N., Kongkaneramit, L., Chen, F., Lu, Y., Jiang, B.-H., Rojanasakul, Y. (2008). The Fas Death Signaling Pathway Connecting Reactive Oxygen Species Generation and FLICE Inhibitory Protein Down-Regulation. J. Immunol. 180: 3072-3080 [Abstract] [Full Text]  
• Prabhakar, B. S., Mulherkar, N., Prasad, K. V. (2008). Role of IG20 Splice Variants in TRAIL Resistance. Clin. Cancer Res. 14: 347-351 [Abstract] [Full Text]  
• Du, M-Q, Bacon, C M, Isaacson, P G (2007). Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and lymphoproliferative disorders. J. Clin. Pathol. 60: 1350-1357 [Abstract] [Full Text]  
• Perl, M., Chung, C.-S., Perl, U., Lomas-Neira, J., de Paepe, M., Cioffi, W. G., Ayala, A. (2007). Fas-induced Pulmonary Apoptosis and Inflammation during Indirect Acute Lung Injury. Am. J. Respir. Crit. Care Med. 176: 591-601 [Abstract] [Full Text]  
• Altemeier, W. A., Zhu, X., Berrington, W. R., Harlan, J. M., Liles, W. C. (2007). Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway. J. Leukoc. Biol. 82: 721-728 [Abstract] [Full Text]  
• Rae, C., Langa, S., Tucker, S. J., MacEwan, D. J. (2007). Elevated NF-{kappa}B responses and FLIP levels in leukemic but not normal lymphocytes: reduction by salicylate allows TNF-induced apoptosis. Proc. Natl. Acad. Sci. USA 104: 12790-12795 [Abstract] [Full Text]  
• Izawa, T., Ishimaru, N., Moriyama, K., Kohashi, M., Arakaki, R., Hayashi, Y. (2007). Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance. Blood 110: 242-250 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS