PACSIN2 as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells
| Autor: | Giulia Zudeh, Raffaella Franca, Marianna Lucafò, Erik J Bonten, Matteo Bramuzzo, Riccardo Sgarra, Cristina Lagatolla, Martina Franzin, William E Evans, Giuliana Decorti, Gabriele Stocco |
|---|---|
| Přispěvatelé: | Zudeh, Giulia, Franca, Raffaella, Lucafò, Marianna, Bonten, Erik J, Bramuzzo, Matteo, Sgarra, Riccardo, Lagatolla, Cristina, Franzin, Martina, Evans, William E, Decorti, Giuliana, Stocco, Gabriele |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
pharmacogenomics
personalized therapy lymphoid cells autophagy pediatric patients pharmacogenomic Ecology thiopurines Health Toxicology and Mutagenesis PACSIN2 intestinal cells Plant Science TPMT inflammatory bowel disease Biochemistry Genetics and Molecular Biology (miscellaneous) intestinal cell thiopurine lymphoid cell pediatric patient |
| Popis: | PACSIN2 variants are associated with gastrointestinal effects of thiopurines and thiopurine methyltransferase activity through an uncharacterized mechanism that is postulated to involve autophagy. This study aims to clarify the role of PACSIN2 in autophagy and in thiopurine cytotoxicity in leukemic and intestinal models. Higher autophagy and lower PACSIN2 levels were observed in inflamed compared with non-inflamed colon biopsies of inflammatory bowel disease pediatric patients at diagnosis. PACSIN2 was identified as an inhibitor of autophagy, putatively through inhibition of autophagosome formation by a protein–protein interaction with LC3-II, mediated by a LIR motif. Moreover, PACSIN2 resulted a modulator of mercaptopurine-induced cytotoxicity in intestinal cells, suggesting that PACSIN2-regulated autophagy levels might influence thiopurine sensitivity. However, PACSIN2 modulates cellular thiopurine methyltransferase activity via mechanisms distinct from its modulation of autophagy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|