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]

Karawajew, L. et al.

Karawajew, Rhein, Czerwony, Ludwig,

Stress-induced activation of the p53 tumor suppressor in leukemia cells and normal lymphocytes requires mitochondrial activity and reactive oxygen species.

The p53 system is highly stress sensitive and integrates diverse intracellular signals in a complex and poorly defined manner. We report on the high dependence of stress-induced p53 activation on mitochondrial activity. Down-regulation of mitochondrial transmembrane potential (MTMP) by inhibitors of electron transport (rotenone, thenoyltrifluoroacetone (TTFA)) and adenosine triphosphate (ATP) synthesis (oligomycin) prevented stress-induced p53 protein accumulation and abrogated p53-dependent apoptosis in a wild-type p53 leukemia cell line MOLT-3, in primary leukemia cells and in normal T lymphocytes. Using genome-wide gene expression analysis, stress-induced up-regulation of the p53 transcriptional targets and their specific inhibition by oligomycin has been demonstrated. Oligomycin did not impair p53-independent apoptosis and caused only a slight reduction of intracellular ATP levels. Reactive oxygen species (ROS) localized to mitochondria decreased in the presence of oligomycin, and stress-induced p53 activation showed strong ROS sensitivity both in leukemic and normal cells. These observations identify mitochondrial activity, described by MTMP and ROS levels, as a critical intracellular determinant of the p53 stress sensitivity and suggest potential implications of this linkage in the mechanisms of chemoresistance of acute leukemia cells.[1]

References

Stress-induced activation of the p53 tumor suppressor in leukemia cells and normal lymphocytes requires mitochondrial activity and reactive oxygen species. Karawajew, L., Rhein, P., Czerwony, G., Ludwig, W.D. Blood (2005) [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.