2 resultados para 181-1123

em Consorci de Serveis Universitaris de Catalunya (CSUC), Spain


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With the aim of preserving artistic heritage, museums have typically removed paintings and furniture from the places they were created for. Over the decades, the curators of these places have begun to request that these artistic works be returned, conscious of the significance that many of these works now have. Some institutions and museums have responded to these requests by providing copies of the original works. Although traditionally these copies were handmade, digital resources, such as audiovisual technology, are now being used. The Taüll 1123 project (Lleida, Spain) is an example of the use of these new tools for the benefit of artistic heritage and of modern visitors.

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KRAS phosphorylation has been reported recently to modulate the activity of mutant KRAS protein in vitro. In this study, we defined S181 as a specific phosphorylation site required to license the oncogenic function of mutant KRAS in vivo. The phosphomutant S181A failed to induce tumors in mice, whereas the phosphomimetic mutant S181D exhibited an enhanced tumor formation capacity, compared with the wild-type KRAS protein. Reduced growth of tumors composed of cells expressing the nonphosphorylatable KRAS S181A mutant was correlated with increased apoptosis. Conversely, increased growth of tumors composed of cells expressing the phosphomimetic KRAS S181D mutant was correlated with increased activation of AKT and ERK, two major downstream effectors of KRAS. Pharmacologic treatment with PKC inhibitors impaired tumor growth associated with reduced levels of phosphorylated KRAS and reduced effector activation. In a panel of human tumor cell lines expressing various KRAS isoforms, we showed that KRAS phosphorylation was essential for survival and tumorigenic activity. Furthermore, we identified phosphorylated KRAS in a panel of primary human pancreatic tumors. Taken together, our findings establish that KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors.