SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during...

The sirtuin proteins are an evolutionarily conserved family of NAD+-dependent deacetylases that regulate various cellular functions. Among the seven sirtuins, SIRT2 is predominantly found in the cytoplasm, and is present in a wide range of tissues. Recent studies indicate that SIRT2 plays an important role in metabolic homeostasis. Several studies indicate that SIRT2 is upregulated under serum deprivation conditions. Since the serum response factor gene usually responds rapidly to serum deprivation and/or serum restoration following deprivation, we hypothesized that a common mechanism may serve to regulate both SIRT2 and SRF during serum stimulation. Using a bioinformatics approach, we searched the SRF binding motif in the SIRT2 gene, and found one classic CArG element (CCATAATAGG) in the SIRT2 gene promoter, which was bound to SRF in the electrophoretic mobility shift assay (EMSA). Serum deprivation induced SIRT2 expression, while SRF and the SRF binding protein, p49/STRAP, repressed SIRT2 gene expression. SIRT2 gene expression was also repressed by the Rho/SRF inhibitor, CCG-1423. These data demonstrate that the classic SRE element in the SIRT2 gene promoter region is functional and therefore, SIRT2 gene is a downstream target of the Rho/SRF signaling pathway. The increased expression of SRF that was observed in the aged heart may affect SIRT2 gene expression and contribute to altered metabolic status in senescence.