Interferon (IFN) ␣ induces a caspase-dependent apoptosis that is associated with activation of the proapoptotic Bak and Bax, loss of mitochondrial membrane potential, and release of cytochrome c. In addition to the onset of the classical Jak-STAT pathway, IFN␣ also induced phosphoinositide 3-kinase (PI3K) activity. Pharmacological inhibition of PI3K activity by Ly294002 disrupted IFN-induced apoptosis upstream of mitochondria. Inhibition of mTOR by rapamycin or by overexpression of a kinase dead mutant of mTOR, efficiently blocked IFN␣-induced apoptosis. A PI3K and mTOR-dependent phosphorylation of p70S6 kinase and 4E-BP1 repressor was induced by IFN␣ treatment of cells and was strongly inhibited by Ly294002 or rapamycin. The activation of Jak-STAT signaling upon IFN␣ stimulation was not affected by abrogating PI3K/mTOR pathway. Neither was the expression of several IFN␣ target genes affected, nor the ability of IFN␣ to protect against virus-induced cell death affected by inhibition of the PI3K/mTOR pathway. These data demonstrate that an intact PI3K/ mTOR pathway is necessary for the ability of IFN␣ to induce apoptosis, whereas activation of the Jak-STAT pathway alone appears to be insufficient for this specific IFN␣-induced effect.

Interferon (IFN)␣ induces apoptosis via Bak and

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Analysis of the literature reporting p53 mutations shows that 8% of report display typographical mistakes with a notable increase in recent years. These errors are sometimes isolated, but in some cases, they concern several or even all mutations described in a single article. Furthermore, some works report unusual profile of p53 mutations whose accuracy is difficult to assess. To handle these problems we have developed MUT-TP53 2.0, an accurate and powerful tool that will automatically handle p53 mutations and generate tables ready for publication that will lower the risk of typographical errors. Furthermore, using functional and statistical information issued from the UMD p53 database, it allows to assess the biological activity and the likelihood of every p53 mutant.

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