Autophagy-induced senescence is regulated by p38α signaling

• DOI: 10.1038/s41419-019-1607-0
• Publication Date: 2019-05-15T11:05:22Z
• Authors: Konstantin Slobod...; Nevenka Radic; Saška Ivanova; Anna Llado; Natalia Trempolec; Antonio Zorzano; Angel R. Nebreda
• Keywords: Senescence; Cell fate determination; Autophagosome

Abstract Apoptosis and senescence are two mutually exclusive cell fate programs that can be activated by stress. The factors instruct cells to enter into or apoptosis not fully understood, but both regulated the stress kinase p38α. Using an inducible system specifically activates this pathway, we show sustained p38α activation suffices trigger massive autophagosome formation enhance basal autophagic flux. This requires concurrent effect of increased mitochondrial reactive oxygen species production phosphorylation ULK1 on Ser-555 Moreover, demonstrate macroautophagy induction signaling determines cancer preferentially instead undergoing apoptosis. In agreement with these results, present evidence autophagy protects from chemotherapy-induced promoting senescence. Our results identify a new mechanism p38α-regulated controls in response