VMP1 is a inducible gene which activation is a switch for autophagy

LO RE AE; MOLEJON MI; ROPOLO A; BOGGIO V; VACCARO MI

Congreso; Experimental Biology 2012; 2012

Autophagy is an evolutionarily preserved degradation process of cytoplasmic cellular constituents, which participates in cell homeostasis as well as in response to disease. Autophagy acts in a myriad of cellular events leading to survival or cell death.The aim of this work was to study the effector molecules that regulate the transcription of the inducible gene vmp1, which expression triggers autophagy. Using a combination of luciferase assays, expression analysis and shRNA strategies, we report the identification of the promoter region of the human vmp1 gene and the molecular pathways that lead to its activation. We show that vmp1 promoter responds to autophagy stimuli through mTOR-dependent and mTOR-independent pathways. Besides we present the essential sequence required for this activation containing the TATA Box and several consensus binding sites for transcription factors related to the cellular stress such as CREB, E2F1, c-Jun and c-Fos. We demonstrate that overexpression of any of this factors induces VMP1 expression. Moreover using shRNA technology, p62 degradation and LC3 cleavage or recruitment we show that these factors induce VMP1-mediated autophagy.Finally we found that p300 acts and is required as a coactivator for VMP1 activation and autophagy. Our results define VMP1 as a target for cellular stress mediators, which activation is a switch for autophagy.