The MEK/ERK pathway is essential for maintenance of cytoprotective autophagy in E1A+cHA-RAS transformants after exposure to radiation

Abstract

Autophagy is a conserved process of protein and organelle degradation that serves to maintain cell viability. Autophagy is frequently induced in response to stress or to exposure to DNA-damaging agents or retinoids, as well as to starvation and deficiency of growth factors. In this work, autophagy induced in E1A+cHA-RAS transformed cells in response to X-ray radiation was studied, with a focus on the role of the MEK/ERK signaling pathway in the regulation of radiation-induced autophagy. It was found that inhibition of the MEK/ERK pathway diminished cell viability and altered the sequence of events in radiation-induced autophagy. In particular, it caused aberrations in its final stages, leading to cytoplasmic accumulation of the p62/SQSTM1 adaptor protein in autophagic cavities of unclear origin. Thus, the MEK/ERK pathway activity is essential for the induction and maintenance of autophagy, increasing the viability of exposed cells in response to radiation.