G-protein gamma subunit GNG11 strongly regulates cellular senescence.

GNG11 is a member of the gamma subunit family of heteromeric G-protein, but its function is entirely unknown. Here, we successfully characterized its specific role in cellular senescence. We have found that overexpression of GNG11 immediately induces cellular senescence in normal human fibroblasts, and its down-regulation by antisense cDNA extends their lifespan. Surprisingly, this gene is very rapidly induced by senescence-inducing agents such as H(2)O(2). Furthermore, overexpression of GNG11 activated ERK1/2 of the MAP kinase family, but did not Ras. Collectively, these results suggest a novel senescence pathway mediated by GNG11 in response to environmental cues.