{"product_id":"molecular-mechanisms-induced-by-p53-reactivating-molecules-von-claudia-fiorini","title":"Molecular mechanisms induced by p53 reactivating molecules","description":"\u003cp\u003eTP53 gene mutations compromising p53 transcriptional function occur in more than 50% of human cancers, including pancreatic adenocarcinoma, and render cancer cells more resistant to conventional therapy. In the last few years, many efforts have been addressed to identify p53-reactivating molecules able to restore the wild-type transcriptionally competent conformation of the mutated proteins. In the present thesis, we show that two of these compounds, CP-31398 and RITA, can induce cell growth inhibition, apoptosis, and autophagy by activating p53\/DNA binding and p53 phosphorylation (Ser15), without affecting the total amount of p53. These effects occur in both wild-type and mutant p53 (mutp53) pancreatic adenocarcinoma cell lines, whereas they are much less pronounced in normal human primary fibroblasts. Furthermore, CP-31398 and RITA regulate the axis SESN1- 2\/AMPK\/mTOR by inducing AMPK phosphorylation in Thr172, which has a crucial role in the autophagic response.Our results support the development of an anti-tumoral strategy based on autophagy inhibition associated to the combined treatment of p53-reactivating molecules with standard chemotherapy,for both wild-type and mutant p53\u003c\/p\u003e\u003cdiv class=\"aw-variant-hidden-subtitle-div\" id=\"aw-variant-subtitle-9783639667332\"\u003e\u003ch3\u003eMolecular mechanisms induced by p53 reactivating molecules in p53 mutant pancreatic cancer cell lines\u003c\/h3\u003e\u003c\/div\u003e","brand":"Autorenwelt Shop","offers":[{"title":"Softcover - 9783639667332","offer_id":39467118428253,"sku":"9783639667332","price":45.9,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0940\/0622\/files\/43b6fa10-b4c7-489f-a488-e0a7d4a6a933.jpg?v=1769837557","url":"https:\/\/shop.autorenwelt.de\/products\/molecular-mechanisms-induced-by-p53-reactivating-molecules-von-claudia-fiorini","provider":"Autorenwelt Shop","version":"1.0","type":"link"}