Title:Gas1 is a Pleiotropic Regulator of Cellular Functions: from Embryonic Development to Molecular Actions in Cancer Gene Therapy
Volume: 14
Issue: 14
Author(s): Jose Segovia and Natanael Zarco
Affiliation:
Keywords:
Akt, apoptosis, GDNF, growth arrest, Shh.
Abstract: Cellular homeostasis is governed by a precise regulation of the molecular mechanisms of action of several
proteins in a given time. There is a group of proteins that have a particular role depending on the cellular context in which
they are present and are known as pleiotropic proteins. The Gas1 (Growth Arrest Specific 1) gene was isolated from a
subtraction library from serum arrested versus growing NIH3T3 mouse fibroblast. Gas1 is a member of the alpha
receptors (GFRα) for the family of GDNF ligands (GFL), we have previously shown that Gas1 acts as a negative
modulator of the GDNF-induced intracellular signaling and induces cell arrest and apoptosis. This modulating activity is
the cause of the capacity of Gas1 to act as a tumor suppressor. On the other hand, several studies have shown the
interaction between Gas1 and Hh (Hedgehog) proteins to potentiate the positive regulation of this pathway, which is
involved in the development of the nervous system, and in both the origin and progression of different tumors. This
review summarizes our current understanding of the structure of Gas1 and the molecular mechanism of action in different
cellular functions, both during embryonic development, in the adult and its effects inhibiting cell growth and inducing
apoptosis of cancer cells.
