Autophagy as a cell fate determinant facing drugs and trophic-nutritional deprivation
Universitat de Lleida. Departament de Medicina Experimental
MetadataShow full item record
The 1st part of the thesis demonstrates that autophagy promotes cell death by an intrinsic apoptotic pathway at the early times of trophic-nutritional deprivation. In this paradigm, autophagy also promotes apoptosis induced by anticancer drugs. At longer times, autophagy displays its assumed protective role on starved cells. Time, being the only determinant of the dual role of autophagy on cell fate, is a novelty that impinges on tumor biology and therapy. The 2nd part of the thesis focuses on the compound 2-phenylethynesulfonamide (PES) with a promising lethal selectivity for cancer cells, already published. PES is an inhibitor of Heat Shock Protein 70 and autophagy, thus impairing cell proteostasis. The thesis reveals a positive feed-back between reactive oxygen species and p53 in the PES mode of action. Finally, PES uncovers an unexpected pro-survival function of BAX protein, precisely the promotion of mitochondrial fusion.
European research projects
- Tesis Doctorals 
Showing items related by title, author, creator and subject.
Das, Arindam (Universitat de Lleida, 2012-07-18)
Anàlisi dels mecanismes moleculars implicats en els processos de mort cel·lular causats per Roscovitina i 7-Bromoindirubina-3'-Oxima(7BIO) Garrofé Ochoa, Xènia (Universitat de Lleida, 2010-10-28)
Mattiolo, Paolo; Yuste Mateos, Víctor J. (Víctor José); Boix Torras, Jacint; Ribas i Fortuny, Judit (Elsevier, 2015-12)Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and ...