Large-Scale RNAi Screens to Dissect TNF and NF-κB Signaling Pathways

  • Marie Metzig
  • Dorothee Nickles
  • Michael Boutros
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


TNFR signaling and activation of NF-κB plays a central role in balancing tissue homeostasis. Aberrant regulation of this signaling pathway contributes to many human diseases, including cancer, neurodegeneration, and pathogenic infections. Much effort is currently spent on investigations to understand its regulation and to define new targets for therapeutic interventions. In this chapter, we review large-scale RNAi screening approaches as a powerful tool for the dissection of signaling pathways. Using the example of a recently performed screen for novel regulators of TNFα/NF-κB signaling among the family of human deubiquitinating enzymes (DUBs), we summarize requirements for setting up a screen and the follow-up of candidate genes. In conclusion we give an overview about current therapeutic options targeting TNFα signaling and discuss the relevance of target discovery by RNAi for progress in cancer therapy.


RNAi Screen TNFR1 Signaling RNAi Screening Hemorrhagic Tumor Necrosis Cylindromatosis Tumor Suppressor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Christina Falschlehner for critical comments on the manuscript. M.M. was supported by fellowships from the Studienstiftung and the F.C. Behr foundation. Research in the laboratory of M.B. is supported by grants from the European Commission, BMBF, EMBO and the DFG.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Marie Metzig
    • 1
  • Dorothee Nickles
    • 1
  • Michael Boutros
    • 2
  1. 1.Division of Signaling and Functional GenomicsGerman Cancer Research Center (DKFZ), University of HeidelbergHeidelbergGermany
  2. 2.Division of Signaling and Functional Genomics, Medical Faculty MannheimGerman Cancer Research Center (DKFZ) and University of HeidelbergHeidelbergGermany

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