scholarly journals KSHV vFLIP Is Essential for the Survival of Infected Lymphoma Cells

2004 ◽  
Vol 199 (7) ◽  
pp. 993-1003 ◽  
Author(s):  
Ilaria Guasparri ◽  
Shannon A. Keller ◽  
Ethel Cesarman
Keyword(s):  
Interleukin 1 ◽  
Nuclear Factor ◽  
Converting Enzyme ◽  
Inhibitory Protein ◽  
Enhanced Sensitivity ◽  
Latently Infected ◽  
Induction Of Apoptosis ◽  
Primary Effusion Lymphomas ◽  
Cellular Flip ◽  
Infected Tumor

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)–κB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-β–converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-κB more potently than cellular FLIP in B cells and that it is largely responsible for NF-κB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-κB activity, down-regulation of essential NF-κB–regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.

scholarly journals Abundant c-Fas–associated death domain–like interleukin-1–converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death

Blood ◽  
2009 ◽  
Vol 114 (5) ◽  
pp. 1026-1028 ◽  
Author(s):  
Yu Yu ◽  
Cristina Iclozan ◽  
Tomohide Yamazaki ◽  
Xuexian Yang ◽  
Claudio Anasetti ◽  
...  
Keyword(s):  
Cell Death ◽  
Th17 Cells ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Interleukin 17 ◽  
Death Domain ◽  
Converting Enzyme ◽  
T Helper ◽  
Inhibitory Protein ◽  
Activation Induced Cell Death

Activation-induced cell death (AICD) plays an important role in peripheral T-cell tolerance. AICD in CD4 T helper (Th) cells, including Th1 and Th2 effectors, has been extensively studied. Recently, interleukin-17–producing CD4+ T cells (Th17 cells) have been identified as a unique Th subset, but their susceptibility to AICD and the underlying molecular mechanisms have not been defined. In this study, we found that Th17 cells were significantly less susceptible to AICD than Th1 cells, and Th17 cell resistance to AICD is due to the high levels of c-Fas–associated death domain–like interleukin-1–converting enzyme inhibitory protein preventing Fas-mediated apoptosis. The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy.

scholarly journals Purification and characterization of active human interleukin-1 beta-converting enzyme from THP.1 monocytic cells.

1993 ◽  
Vol 268 (24) ◽  
pp. 18062-18069 ◽  
Author(s):  
D.K. Miller ◽  
J.M. Ayala ◽  
L.A. Egger ◽  
S.M. Raju ◽  
T.T. Yamin ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Converting Enzyme ◽  
Purification And Characterization ◽  
Monocytic Cells

scholarly journals Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.

1994 ◽  
Vol 269 (30) ◽  
pp. 19331-19337 ◽  
Author(s):  
T. Komiyama ◽  
C.A. Ray ◽  
D.J. Pickup ◽  
A.D. Howard ◽  
N.A. Thornberry ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Cowpox Virus ◽  
Interleukin 1 Beta ◽  
Converting Enzyme

scholarly journals A novel splice variant of mouse interleukin-1-receptor-associated kinase-1 (IRAK-1) activates nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)

2003 ◽  
Vol 370 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Ken YANAGISAWA ◽  
Kenji TAGO ◽  
Morisada HAYAKAWA ◽  
Motomichi OHKI ◽  
Hiroyuki IWAHANA ◽  
...  
Keyword(s):  
Splice Variant ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Tumour Necrosis Factor Receptor ◽  
Acceptor Site ◽  
Nuclear Factor ◽  
Death Domain ◽  
Signalling Molecule ◽  
Novel Variant ◽  
Nf Kappab

Interleukin-1 (IL-1)-receptor-associated kinase (IRAK) is an indispensable signalling molecule for host-defence responses initiated by a variety of ligands that bind to members of the Toll/IL-1 receptor family. Here we report a novel splice variant of mouse IRAK-1, IRAK-1-S, which is generated by utilizing a new splicing acceptor site within exon 12. IRAK-1-S cDNA is shorter than the originally reported IRAK-1 (IRAK-1-W) cDNA by 271 nucleotides, and the subsequent frameshift causes a premature termination of translation after 23 amino acids, which are unique to the IRAK-1-S protein. To elucidate the physiological function of IRAK-1-S, we overexpressed it in 293T cells and studied the effects on the IL-1 signalling cascade. As it lacks the C-terminal region of IRAK-1-W that has been reported to contain the TRAF6 (tumour necrosis factor receptor-associated factor 6) binding domain, IRAK-1-S was unable to bind TRAF6 protein, which is a proposed downstream signalling molecule. However, IRAK-1-S overexpressed in 293T cells induced constitutive activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) independent of stimulation by IL-1, as did IRAK-1-W. To clarify the mechanism of NF-κB activation by IRAK-1-S in the absence of binding to TRAF6, we demonstrated that IRAK-1-S binds to IRAK-1-W through its death domain; the findings suggested that overexpressed IRAK-1-S may bind endogenous IRAK-1-W and activate TRAF6 through IRAK-1-W. These results also indicate that this novel variant may play roles in the activation of NF-κB and JNK by IL-1 and other ligands whose signal transduction is dependent on IRAK-1 under physiological conditions.

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