IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner

Slotta C, Storm J, Pfisterer N, Henkel E, Kleinwächter S, Pieper M, Ruiz-Perera L, Greiner J, Kaltschmidt B, Kaltschmidt C (2018)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1865(8): 1025-1033.

Zeitschriftenaufsatz | Veröffentlicht| Englisch
 
Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Autor/in
Slotta, CarstenUniBi; Storm, Jonathan; Pfisterer, Nina; Henkel, Elena; Kleinwächter, Svenja; Pieper, Maren; Ruiz-Perera, Lucia; Greiner, JohannesUniBi ; Kaltschmidt, BarbaraUniBi; Kaltschmidt, ChristianUniBi
Abstract / Bemerkung
TNF signaling is directly linked to cancer development and progression. A broad range of tumor cells is able to evade cell death induced by TNF impairing the potential anti-cancer value of TNF in therapy. Although sensitizing cells to TNF-induced death therefore has great clinical implications, detailed mechanistic insights into TNF-mediated human cell death still remain unknown. Here, we analyzed human cells by applying CRISPR/Cas9n to generate cells deficient of IKK1, IKK2, IKK1/2 and RELA. Despite stimulation with TNF resulted in impaired NF-κB activation in all genotypes compared to wildtype cells, increased cell death was observable only in IKK1/2-double-deficient cells. Cell death could be detected by Caspase-3 activation and binding of Annexin V. TNF-induced programmed cell death in IKK1/2−/− cells was further shown to be mediated via RIPK1 in a predominantly apoptotic manner. Our findings demonstrate the IKK complex to protect from TNF-induced cell death in human cells independently to NF-κB RelA suggesting IKK1/2 to be highly promising targets for cancer therapy.
Stichworte
poptosis; Cell death; IKK; NF-kappa-B; RIPK1; Tumor necrosis factor
Erscheinungsjahr
2018
Zeitschriftentitel
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Band
1865
Ausgabe
8
Seite(n)
1025-1033
ISSN
0167-4889
Page URI
https://pub.uni-bielefeld.de/record/2919162

Zitieren

Slotta C, Storm J, Pfisterer N, et al. IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2018;1865(8):1025-1033.
Slotta, C., Storm, J., Pfisterer, N., Henkel, E., Kleinwächter, S., Pieper, M., Ruiz-Perera, L., et al. (2018). IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1865(8), 1025-1033. doi:10.1016/j.bbamcr.2018.04.003.
Slotta, C., Storm, J., Pfisterer, N., Henkel, E., Kleinwächter, S., Pieper, M., Ruiz-Perera, L., Greiner, J., Kaltschmidt, B., and Kaltschmidt, C. (2018). IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1865, 1025-1033.
Slotta, C., et al., 2018. IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1865(8), p 1025-1033.
C. Slotta, et al., “IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner”, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol. 1865, 2018, pp. 1025-1033.
Slotta, C., Storm, J., Pfisterer, N., Henkel, E., Kleinwächter, S., Pieper, M., Ruiz-Perera, L., Greiner, J., Kaltschmidt, B., Kaltschmidt, C.: IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1865, 1025-1033 (2018).
Slotta, Carsten, Storm, Jonathan, Pfisterer, Nina, Henkel, Elena, Kleinwächter, Svenja, Pieper, Maren, Ruiz-Perera, Lucia, Greiner, Johannes, Kaltschmidt, Barbara, and Kaltschmidt, Christian. “IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner”. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1865.8 (2018): 1025-1033.

5 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

NFκB and Kidney Injury.
Song N, Thaiss F, Guo L., Front Immunol 10(), 2019
PMID: 31040851
A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells.
Kaltschmidt C, Banz-Jansen C, Benhidjeb T, Beshay M, Förster C, Greiner J, Hamelmann E, Jorch N, Mertzlufft F, Pfitzenmaier J, Simon M, Schulte Am Esch J, Vordemvenne T, Wähnert D, Weissinger F, Wilkens L, Kaltschmidt B., Cancers (Basel) 11(5), 2019
PMID: 31083587
Subunit-Specific Role of NF-κB in Cancer.
Kaltschmidt B, Greiner JFW, Kadhim HM, Kaltschmidt C., Biomedicines 6(2), 2018
PMID: 29673141

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 29630899
PubMed | Europe PMC

Suchen in

Google Scholar