Abstracts Biological Sciences

G0S2 impairs ATGL activity and cell cycle progression in murine liver

by Reddy Chakkarappan Sundaram

The G0/G1 switch gene 2 (G0s2) has putative roles in cellular proliferation and fat metabolism. While activated blood mononuclear cells increase the expression of G0S2, cancer cells silence it by promoter methylation. Moreover, G0S2 was shown to act as a proapoptotic factor and recently as an inhibitor of the adipose triglyceride lipase (ATGL) in cell cuture studies. Nonetheless, the role of G0S2 in an in vivo setting remains elusive. Here I describe the characterization of a novel G0s2 knockout mouse model. G0s2 knockout mice are born at expected mendelian ratio and develop normally under normal and high fat diet feeding conditions. Liver regeneration is improved in mice with G0s2 deletion under starvation conditions. Improved cell cycle re-entry in G0s2 knockout livers after partial hepatectomy is associated with decreased triglyceride deposition and lipid droplet formation after 20h of starvation. Supporting the notion of G0S2 acting as a cell cycle inhibitor under certain conditions, over-expression of G0S2 in the hematopoietic system improves stem cell function and hematopoietic reconstitution by maintaining stem cell quiescence and inhibiting their depletion during serial transplantation. This data suggests that G0S2 has cell-cycle regulatory functions in liver and hematopoietic system possibly involving its role in modulating fat metabolism in mice starvation.