|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2011-6-1
|
|
pubmed:abstractText |
Actin cytoskeleton has been shown to play a regulating role in several signaling pathways, and disruption of actin filament has been reported to increase sTNF-?-induced cell death. However, whether actin is involved in tmTNF-?-mediated cytotoxicity remains unclear. Here, we demonstrated that pretreatment of HL-60 with CytD or LatA to depolymerize actin significantly suppressed tmTNF-?-mediated apoptosis. Interestingly, tmTNF-? increased the actin immunoprecipitated by anti-TNFR2 but not anti-TNFR1 antibody, and disruption of the actin filament totally blocked this effect. In addition, TNFR1 knockdown by siRNA did not affect tmTNF-?-mediated cytotoxicity and the inhibitory effect of CytD, suggesting that the involvement of actin in the tmTNF-?-induced apoptosis is linked to the TNFR2 pathway. Our results revealed further that tmTNF-? signaled the inhibition of I?B degradation and NF-?B activity by recruiting RIP1 to and uncoupling TRAF2 from the TNFR2 complex. Nevertheless, CytD totally reversed the tmTNF-? signaling and activated NF-?B by recruiting TRAF2 to and dissociating RIP1 from the TNFR2 complex. Furthermore, tmTNF-? led to activation of caspase-8 by dissociation of cFLIP from TNFR2 and inhibition of the cFLIP expression. Activated caspase-8 cleft RIP1 to suppress NF-?B activity and also mediated tmTNF-?-induced apoptosis. However, CytD blocked the tmTNF-?-induced uncoupling of cFLIP from TNFR2 and prevented caspase-8 activation and the resulting cleavage of RIP1, converting the signaling for tmTNF-?-mediated apoptosis into one for activating NF-?B to survive. These results suggest that the actin cytoskeleton functions in transmitting signals via TNFR2 to mediate tmTNF-?-induced apoptosis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AGFG1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin D,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Pore Complex Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/latrunculin A
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
1938-3673
|
|
pubmed:author |
pubmed-author:FUSTBB,
pubmed-author:GaoTaoT,
pubmed-author:LiQingfenQ,
pubmed-author:LiZhuoyaZ,
pubmed-author:LiuLiliL,
pubmed-author:LiuNaN,
pubmed-author:WIRTR DRD,
pubmed-author:WangJingJ,
pubmed-author:YangKunK,
pubmed-author:YinBingjiaoB,
pubmed-author:ZAKR LRL,
pubmed-author:ZakTT,
pubmed-author:ZhangHailongH
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
89
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
917-26
|
|
pubmed:meshHeading |
pubmed-meshheading:21402772-Actins,
pubmed-meshheading:21402772-Animals,
pubmed-meshheading:21402772-Apoptosis,
pubmed-meshheading:21402772-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:21402772-Blotting, Western,
pubmed-meshheading:21402772-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:21402772-Caspase 8,
pubmed-meshheading:21402772-Cell Membrane,
pubmed-meshheading:21402772-Cytochalasin D,
pubmed-meshheading:21402772-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:21402772-Flow Cytometry,
pubmed-meshheading:21402772-HL-60 Cells,
pubmed-meshheading:21402772-Humans,
pubmed-meshheading:21402772-I-kappa B Proteins,
pubmed-meshheading:21402772-Immunoprecipitation,
pubmed-meshheading:21402772-Interleukin-8,
pubmed-meshheading:21402772-Mice,
pubmed-meshheading:21402772-NF-kappa B,
pubmed-meshheading:21402772-NIH 3T3 Cells,
pubmed-meshheading:21402772-Nuclear Pore Complex Proteins,
pubmed-meshheading:21402772-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:21402772-RNA, Messenger,
pubmed-meshheading:21402772-RNA, Small Interfering,
pubmed-meshheading:21402772-RNA-Binding Proteins,
pubmed-meshheading:21402772-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:21402772-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:21402772-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21402772-Signal Transduction,
pubmed-meshheading:21402772-Thiazolidines,
pubmed-meshheading:21402772-Tumor Necrosis Factor-alpha
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
The involvement of ?-actin in the signaling of transmembrane TNF-?-mediated cytotoxicity.
|
|
pubmed:affiliation |
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
