INVESTIGADORES
ROPOLO Alejandro Javier
congresos y reuniones científicas
Título:
VMP1 is a novel inducible gene which activation is a switch for autophagy.
Autor/es:
LO RE, A.; MOLEJÓN, M. I.; ALEJANDRO JAVIER ROPOLO; BOGGIO, V.; VACCARO, M. I.
Lugar:
San Diego, CA.
Reunión:
Congreso; Experimental Biology; 2012
Institución organizadora:
The American Society For Biochemistry and Molecular Biology
Resumen:
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. AL:CONICET;MIV:UBA- CONICET- ANPCyT.