Growth-arrest-specific 2 gene was originally identified in murine fibroblasts under growth arrest conditions.
Serum stimulation of quiescent, non-dividing cells leads to the down-regulation of gas2 and results in re-entry into the cell cycle.
Gas2 protein has been shown to co-localize with actin and microtubules in interphase mammalian cells which helps in cytoskeleton rearrangement during cell cycle and cell division.
During apoptosis, Gas2 is specifically cleaved at its C-terminus by a still unknown ICE-like protease, and the processed protein induces dramatic rearrangements in the cytoskeleton when overexpressed in several cell types.
The protein encoded by this gene is a caspase-3 substrate.
It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.
In humans, it is expressed in most tissues. Highest levels in liver, lung and kidney. In the embryo strongly expressed in regions that undergo extensive apoptosis, such as the intervertebral tissues, the cranofacial mesenchyme and the cartilage of the limbs. The overexpression of Gas2 efficiently increases cell susceptibility to apoptosis following UV irradiation, etoposide and methyl methanesulfonate treatments, and that these effects are dependent on increased p53 stability and transcription activity.
Diseases associated with GAS2 include Gnathodiaphyseal Dysplasia. Among its related pathways are GPCR Pathway and Apoptosis and survival Caspase cascade. An important paralog of this gene is GAS2L3.
Post-translational modifications for GAS2 Gene :
Cleaved, during apoptosis, on a specific aspartic residue by caspases.
Phosphorylated on serine residues during the G0-G1 transition phase.
Modification sites at PhosphoSitePlus
Modification sites at neXtProt
According to annotation using interpro, Gas2 may play a role in apoptosis by acting as a cell death substrate for caspases. Is cleaved during apoptosis and the cleaved form induces dramatic rearrangements of the actin cytoskeleton and potent changes in the shape of the affected cells. May be involved in the membrane ruffling process.
Biological process as GO annotation :
The regulation of Gas2 biosynthesis reflects the pattern of mRNA expression. Its relative level is tightly associated with growth arrest. Gas2 seems to be regulated also at the posttranslational level via a phosphorylation mechanism.
External links for further reference :
Growth-Arrest-Specific Protein 2 Inhibits Cell Division in Xenopus Embryos : http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024698
GAS2-Calpain2 axis contributes to the growth of leukemic cells. : https://www.ncbi.nlm.nih.gov/pubmed/26358320/
The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. : https://www.ncbi.nlm.nih.gov/pubmed/11387205/
Growth arrest specific 2 is up-regulated in chronic myeloid leukemia cells and required for their growth. : https://www.ncbi.nlm.nih.gov/pubmed/24465953/
cDNA Characterization and Chromosome Mapping of the Human GAS2 Gene : http://www.sciencedirect.com/science/article/pii/S0888754397951727
Gas2, a growth arrest-specific protein, is a component of the microfilament network system : http://jcb.rupress.org/content/117/6/1251