G0S2, an early response gene, regulates quiescence in naïve T cells (104.10)

Abstract

Abstract The G0/G1 switch gene 2 (G0S2) was identified in a screen using mitogen-activated human blood mononuclear cells (DNA and Cell Biology 9, 579, 1990). G0S2 is a small basic protein expressed in hematopoietic cells that is upregulated in autoimmune and inflammatory processes. However, the ability of G0S2 to control T cell proliferation has yet to be determined. We found that G0S2 transcription was suppressed following TCR activation in naïve T cells, suggesting its role in T cell quiescence. Also, inhibition of MAPK, PI3K, mTOR and Ca2+/calcineurin pathways abrogated G0S2 gene suppression, which suggests that the aforementioned pathways are involved in the suppression of G0S2. Moreover, gain-of function experiments, using retroviral gene transfer and BM transplantation, showed that ectopic G0S2 expression inhibited proliferation of T cells during homeostasis and upon TCR activation. Conversely, silencing G0S2 expression enhanced T cell proliferation, indicating that G0S2 maintains quiescence of naïve T cells. We further identified nucleolin as a protein partner of G0S2 by Co-IP and mass-spectrometry. This data suggests that G0S2 interferes with nucleolin-mediated stabilization of mRNAs of genes required for proliferation control. Collectively, our study uncovered an important role of G0S2 in the mechanism of T cell quiescence.