Akt Regulates TNF? Synthesis Downstream of RIP1 Kinase Activation during Necroptosis

Simple item page
dc.contributor.authorMcNamara, Colleen R.
dc.contributor.authorAhuja, Ruchita
dc.contributor.authorOsafo-Addo, Awo D.
dc.contributor.authorBarrows, Douglas
dc.contributor.authorKettenbach, Arminja
dc.contributor.authorSkidan, Igor
dc.contributor.authorTeng, Xin
dc.contributor.authorCuny, Gregory D.
dc.contributor.authorGerber, Scott A.
dc.contributor.authorDegterev, Alexei
dc.date.accessioned2020-03-10T17:31:07Z
dc.date.available2020-03-10T17:31:07Z
dc.date.issued2013-03
dc.description.abstractNecroptosis is a regulated form of necrotic cell death that has been implicated in the pathogenesis of various diseases including intestinal inflammation and systemic inflammatory response syndrome (SIRS). In this work, we investigated the signaling mechanisms controlled by the necroptosis mediator receptor interacting protein-1 (RIP1) kinase. We show that Akt kinase activity is critical for necroptosis in L929 cells and plays a key role in TNF? production. During necroptosis, Akt is activated in a RIP1 dependent fashion through its phosphorylation on Thr308. In L929 cells, this activation requires independent signaling inputs from both growth factors and RIP1. Akt controls necroptosis through downstream targeting of mammalian Target of Rapamycin complex 1 (mTORC1). Akt activity, mediated in part through mTORC1, links RIP1 to JNK activation and autocrine production of TNF?. In other cell types, such as mouse lung fibroblasts and macrophages, Akt exhibited control over necroptosis-associated TNF? production without contributing to cell death. Overall, our results provide new insights into the mechanism of necroptosis and the role of Akt kinase in both cell death and inflammatory regulation.
dc.identifier.citationCopyright 2013 PLoS One. Recommended citation: McNamara, Colleen R., Ruchita Ahuja, Awo D. Osafo-Addo, Douglas Barrows, Arminja Kettenbach, Igor Skidan, Xin Teng, Gregory D. Cuny, Scott Gerber, and Alexei Degterev. "Akt Regulates TNF? synthesis downstream of RIP1 kinase activation during necroptosis." PLoS One 8, no. 3 (2013): e56576. doi: 10.1371/journal.pone.0056576. URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056576. Reproduced in accordance with the original publisher's licensing terms and with permission from the authors.
dc.identifier.urihttps://hdl.handle.net/10657/5940
dc.language.isoen_US
dc.publisherPLoS One
dc.subjectL929 cells
dc.subjectNecrotic cell death
dc.subjectgrowth factors
dc.subjectsmall interfering RNAs
dc.subjectAutophagic Cell Death
dc.subjectApoptosis
dc.subjectCell Viability testing
dc.subjectPhosphorylation
dc.titleAkt Regulates TNF? Synthesis Downstream of RIP1 Kinase Activation during Necroptosis
dc.typeArticle

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Cuny_2013_AktRegulatesTNFa.pdf
Size:
3.07 MB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.69 KB
Format:
Plain Text
Description:
Download

Collections

UH Faculty, Staff, and Student Works