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]

Peiretti, F. et al.

Peiretti, Lopez, Deprez-Beauclair, Bonardo, Juhan-Vague, Nalbone,

Inhibition of p70(S6) kinase during transforming growth factor-beta 1/vitamin D(3)-induced monocyte differentiation of HL-60 cells allows tumor necrosis factor-alpha to stimulate plasminogen activator inhibitor-1 synthesis.

We investigated intracellular mechanisms involved in the up-regulation of plasminogen activator inhibitor I (PAI-1) synthesis by human recombinant tumor necrosis factor-alpha (TNF) during monocyte differentiation of HL-60 cells triggered by the transforming growth factor-beta1/vitamin D(3) (TGF/D3) mixture. TGF/D3-treated cells expressed surface monocytic markers and produced noticeable amounts of PAI-1 but stopped to proliferate. A reduced p70 S6 kinase (p70(S6K)) phosphorylation was also observed and, in this situation, TNF dramatically enhanced PAI-1 synthesis. Similarly, TNF significantly up-regulated PAI-1 synthesis when p70(S6K) phosphorylation was inhibited by rapamycin. This phenomenon was not due to a general decrease in protein synthesis but involved the activation of gene transcription rather than PAI-1 mRNA stabilization. The level of the transcriptional regulator factor E2F1, a repressor of PAI-1 gene expression, was shown to be down-modulated in TGF/D3- as well as in rapamycin-treated cells. Furthermore, the apoptotic effect of TNF in HL-60 cells appeared to be prevented by the addition of either TGF/D3 or rapamycin. In conclusion, these results indicate that inhibition of p70(S6K) phosphorylation during TGF/D3-induced monocyte differentiation of HL-60 cells is a determinant factor that allows TNF to exert its up-regulating effect on PAI-1 synthesis while protecting cells from apoptosis.[1]

References

Inhibition of p70(S6) kinase during transforming growth factor-beta 1/vitamin D(3)-induced monocyte differentiation of HL-60 cells allows tumor necrosis factor-alpha to stimulate plasminogen activator inhibitor-1 synthesis. Peiretti, F., Lopez, S., Deprez-Beauclair, P., Bonardo, B., Juhan-Vague, I., Nalbone, G. J. Biol. Chem. (2001) [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.