MAGEB2 INVOLVEMENT IN NUCLEOLAR STRESS RESPONSE

LADELFA, M FÁTIMA; SUBERBORDES MELISA; ESCALADA, MICAELA; MONTE, MARTÍN; PASCUCCI, FRANCO A.

Congreso; LXV Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Beside its role in ribosome biogenesis, the nucleolus senses stress and is a central hub for coordinating the stress response. MageB2 is a tumor specific protein with nucleolar localization. Related with its localization, we have previously observed that MageB2 enhances pre-rRNA transcription and ribosome biogenesis.Here we aim to study the involvement of MageB2 in the nucleolar responses to stress.First, we screened MageB2 protein interactors by performing yeast two-hybrid and immunoprecipitation (IP) follow by mass spectrometry assays. Our results, together with reported ones, showed that, beyond MageB2 interactors involved ribosome biogenesis, 34 and 17 out of 213 interactors were related with the GO terms ?Cellular response to stress? (GO:0033554) and ?Regulation of apoptotic signaling pathway? (GO:2001233), respectively, supporting a role of MageB2 in these biological processes.Actinomycin D (ActD) at low concentration inhibits RNA Pol I and induces nucleolar stress, with the consequent redistribution of some nucleolar proteins. Under this condition, we observed that MageB2 relocalized to the nucleoplasm. Besides, MageB2 IP followed by western blot showed that ActD treatment resulted in MageB2 phosphorylation in Tyrosine.We also observed that MageB2 expression correlated with resistance to apoptosis induced by ActD treatment. However, luciferase reporter gene assay of a p53 responsive promoter demonstrated that MageB2 was not able to regulate p53 function. Moreover, IP assays showed no binding between MageB2 and p53. In line with this, siRNA mediated down-regulation of p53 in U24 cells did not affect the resistance effect of MageB2, suggesting that MageB2 confers resistance to ActD in a p53 independent manner.Altogether, this result suggests that nucleolar stress induced by treatment with ActD changes the localization and phosphorylation status of MageB2. Under this condition, MageB2 is able to counteract apoptosis in a p53 independent manner.