Molecular Biology Reports

, Volume 39, Issue 9, pp 8695–8699 | Cite as

TNFα regulates the localization of CD40 in lipid rafts of glioma cells

  • Richa Tewari
  • Saurav Roy Choudhury
  • Veer Singh Mehta
  • Ellora Sen
Article

Abstract

Resistance of glioblastoma multiforme (GBM) to TNFα induced apoptosis is attributed to NFκB activation. As TNF-receptor family member CD40 regulates NFκB activation, we investigated the role of CD40 in NFκB activation in GBM. We observed elevated CD40 levels in human glioma samples as compared to the surrounding normal tissue. Treatment with TNFα elevated CD40 levels in glioma cells and inhibition of CD40 signaling failed to abrogate TNFα induced NFκΒ activity. While TNFα increased the interaction between TRAF2/6, IκBα, IKKα/β in the CD40 signalosome, the level of CD40 in the signalosome remained unaffected upon TNFα treatment. Interestingly, TNFα decreased the spatial localization of CD40 and increased TRAF2/6 co-localization with lipid raft marker Caveolin. As localization of CD40 signalosome in lipid raft is crucial for NFκB activation, TNFα mediated decreased clustering of CD40 in lipid rafts could have possibly contributed to its non-involvement in NFκB activation.

Keywords

TNFα CD40 NFκB Glioma Lipid rafts 

Notes

Acknowledgments

This work was supported by the Innovative Young Biotechnologist Award (IYBA) research grant from the Department of Biotechnology, Government of India, to ES.

Supplementary material

11033_2012_1726_MOESM1_ESM.tif (1 mb)
Supplementary material 1 (TIFF 1067 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Richa Tewari
    • 1
  • Saurav Roy Choudhury
    • 1
  • Veer Singh Mehta
    • 2
  • Ellora Sen
    • 1
  1. 1.National Brain Research CentreManesarIndia
  2. 2.Paras HospitalsGurgaonIndia

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