SIRT1 Mouse Monoclonal Antibody [7-C5-B2]

功能

Sirtuin 1 is a member of the sirtuin family of proteins, homologs of the Sir2 gene in S. cerevisiae. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Sirtuin 1 is downregulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity. Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors. In mammals, SIRT1 has been shown to deacetylate and thereby deactivate the p53 protein. SIRT1 also stimulates autophagy by preventing acetylation of proteins (via deacetylation) required for autophagy as demonstrated in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction. SIRT1 plays a role in activating T helper 17 cells, which contribute to autoimmune disease; efforts to activate SIRT1 therapeutically may trigger or exacerbate autoimmune disease. SIRT1, along with HDAC1 and the AP-1 promoter complex within D1-type dopaminergic medium spiny neurons, appears to be closely involved in the pathogenesis of addiction.

背景文献

1. "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence." Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S., Pelicci P.G., Kouzarides T. EMBO J. 21:2383-2396(2002)

2. "Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin." Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D. Mol. Cell 16:93-105(2004)

序列相似性

Belongs to the sirtuin family. Class I subfamily.

组织特异性

Widely expressed.

翻译后修饰

Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.; Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity). Phosphorylation at Ser-27 implicating MAPK9 is linked to protein stability. There is some ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.; Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).; S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.; Acetylated at various Lys residues. Deacetylated via an autocatalytic mechanism. Autodeacetylation at Lys-238 promotes its protein deacetylase activity.

亚细胞定位

Nucleus, PML body, Cytoplasm.

UNIPROT #

SwissProt: Q96EB6 Human

别名