In vitro study of p300 role in cellular senescence
Authors:
Elisabetta Di Fede (1,2), Antonella Lettieri (1), Silvia Ancona (1), Esi Taci (1), Silvia Castiglioni (1), Elisa Adele Colombo (1), Paolo Grazioli (1), Clara Bernardelli (1), Elena Lesma (1), Stefania Corti (3,4), Alberto Priori (1,2,5), Cristina Gervasini (1,2), Valentina Massa (1,2)
Organisations:
1: Department of Health Sciences, University of Milan, Milan, Italy
2: Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy
3: Dino Ferrari Centre, Department of Pathophysiology and Transplantation, Neuroscience Section, University of Milan, Milan, Italy
4: IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy
5: ASST Santi Paolo e Carlo, San Paolo University Hospital, Milan, Italy
Presenting author:
Elisabetta Di Fede
Exposition date:
Saturday, September 16, 2023
Exposition position:
018/2
Recently, it was reported that p300, a lysine acetyl transferase protein, could represent a driver of senescence, a process involved in both physiological and pathological process (i.e. cancer and neurodegeneration). Thus, to deepening our understanding of p300 role in senescence we performed experiments on lymphoblastoid cell lines (LCLs) obtained from Rubinstein-Taybi syndrome patients carrying EP300 mutations (EP300+/-) and healthy donor (HD). We induced a senescent-phenotype by oxidative stress in both cell lines revealing that EP300+/- cells were less responsive to senescence induction compared to HD LCLs. We validated our results, obtained with a natural model, mimicking the genetic variants using in HD LCLs a specific pharmacological inhibitor of p300, CCS1477. We confirmed in our models that mutations in EP300 or p300 inhibition impair senescence response processes paving the way to implementing new potential therapeutic target for senescence in age-related disorders, that we are currently studying using neuronal and 3D models.
