Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Kashkar, H. et al.

Hamid Kashkar, Anke Deggerich, Jens-Michael Seeger, Benjamin Yazdanpanah, Katja Wiegmann, Dirk Haubert, Carola Pongratz, Martin Krönke,

NF-kappaB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs.

The proteasome inhibitor bortezomib has been shown to possess promising antitumor activity and significant efficacy against a variety of malignancies. Different studies demonstrated that bortezomib breaks the chemoresistance in different tumor cells basically by altering nuclear factor-kappaB (NF-kappaB) activity. NF-kappaB has been shown to be constitutively active in most primary Hodgkin-Reed-Sternberg (H-RS) cells in lymph node sections and in Hodgkin lymphoma (HL) cell lines and was suggested to be a central molecular switch in apoptosis resistance in HL. Here we report a bimodal effect of bortezomib in HL cells. Whereas high-dose bortezomib induced direct cytotoxicity that correlated with decreased NF-kappaB activity, low-dose bortezomib sensitized HL cells against a variety of cytotoxic drugs without altering NF-kappaB action. Strikingly, bortezomib induced marked XIAP down-regulation at the posttranslational level that was independent of the NF-kappaB status. Similarly, RNA interference (RNAi)-mediated XIAP down-regulation generated susceptibility to cytostatic agents. The results identify XIAP as an NF-kappaB-independent target of bortezomib action that controls the chemoresistant phenotype of HL cells.[1]

References

NF-kappaB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs. Kashkar, H., Deggerich, A., Seeger, J.M., Yazdanpanah, B., Wiegmann, K., Haubert, D., Pongratz, C., Krönke, M. Blood (2007) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.