EC 3.5.1 | S. cerevisiae, homolog 1 | SIR2alpha | SIR2L1 | SIR2-like protein 1 | SIRT1 | Sirtuin 1
规格或纯度
无载体,His标签,≥65% (SDS-PAGE),见COA
生化机理
SIRT1 is an NAD+-dependent class III histone deacetylase. It is a member of the sirtuin family of proteins, homologous to the yeast Sir2 protein. It modulates intracellular activities through transcription regulation and functions in several separate cellular functions. SIRT1 deacetylates and inactivates tumor suppressor protein p53, a process regulated by Hypermethylated in Cancer 1 (HIC1) protein to allow cells to bypass apoptosis and survive DNA damage. The level of SIRT1 is significantly elevated in mouse and human prostate cancer. SIRT1 promotes vascular relaxation by activating endothelial nitric oxide synthase. SIRT1 also protects against microgliadependent amyloid-beta toxicity through inhibiting NF-Kappa b signaling.
Post-translational: 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. Ubiquitinated; leading to degradation. Deubiquitinated by USP22; leading to stabilization.
Store at -20°C for 1 year. Avoid freeze/thaw cycle.
图片
Recombinant Human Sirtuin 1/SIRT1 Protein (rp184934) - SDS-PAGE 3 μg/lane of Recombinant Human Sirtuin 1/SIRT1 Protein was resolved with SDS-PAGE under reducing (R) conditions and visualized by Coomassie® Blue staining, showing a band at 76.6 kDa.