Please use this identifier to cite or link to this item: https://doi.org/10.1038/cdd.2010.72
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dc.titleZVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC-MAPKs-AP-1 pathway
dc.contributor.authorWu, Y.-T.
dc.contributor.authorTan, H.-L.
dc.contributor.authorHuang, Q.
dc.contributor.authorSun, X.-J.
dc.contributor.authorZhu, X.
dc.contributor.authorShen, H.-M.
dc.date.accessioned2014-11-25T09:48:11Z
dc.date.available2014-11-25T09:48:11Z
dc.date.issued2011-01
dc.identifier.citationWu, Y.-T., Tan, H.-L., Huang, Q., Sun, X.-J., Zhu, X., Shen, H.-M. (2011-01). ZVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC-MAPKs-AP-1 pathway. Cell Death and Differentiation 18 (1) : 26-37. ScholarBank@NUS Repository. https://doi.org/10.1038/cdd.2010.72
dc.identifier.issn13509047
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/108605
dc.description.abstractIt is intriguing that some pan-caspase inhibitors such as zVAD-fmk (zVAD) are capable of inducing necrotic cell death in a selected group of cells. As earlier reports from our laboratory have ruled out the original notion that zVAD-induced necrosis in mouse fibrosarcoma L929 cells was autophagic cell death, the main objective of this study was thus to determine the underlying mechanism of this form of cell death. In this study, we provided clear evidence that zVAD-induced necroptosis in L929 cells and such cell death is dependent on autocrine production of tumor necrosis factor-α (TNFα) at the transcriptional level. More importantly, we identified that activating protein-1 (AP-1), but not nuclear factor -B, is the transcription factor controlling zVAD-induced TNFα transcription. Moreover, zVAD is able to activate AP-1 through activation of two upstream mitogen-activated kinases (MAPKs), c-Jun N-terminal kinase and extracellular signal-regulated kinase. Finally, we found that protein kinase C is the important upstream signaling molecule in mediating zVAD-induced activation of MAPKs and AP-1, and subsequent autocrine production of TNFα and cell death. Data from this study reveal the molecular mechanisms underlying zVAD-induced necroptosis, an important form of programmed necrotic cell death with increasing understanding of its biological significance in health and diseases. © 2011 Macmillan Publishers Limited All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/cdd.2010.72
dc.sourceScopus
dc.subjectAP-1
dc.subjectautocrine production of TNFα
dc.subjectL929 cells
dc.subjectnecroptosis
dc.subjectPKC
dc.subjectzVAD-fmk
dc.typeArticle
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.contributor.departmentEPIDEMIOLOGY & PUBLIC HEALTH
dc.description.doi10.1038/cdd.2010.72
dc.description.sourcetitleCell Death and Differentiation
dc.description.volume18
dc.description.issue1
dc.description.page26-37
dc.description.codenCDDIE
dc.identifier.isiut000285289900005
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