Cell Signaling Technology

Product Pathways - Chromatin Regulation / Epigenetics

SirT3 (D22A3) Rabbit mAb #5490

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H M R Endogenous 28 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

SirT3 (D22A3) Rabbit mAb detects endogenous levels of total SirT3 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val130 of mouse SirT3 protein.

Western Blotting

Western Blotting

Western blot analysis of mitochondrial extracts from SirT3 wild-type (WT) and knockout (KO) mouse liver, and of whole cell extracts from rat liver and human kidney, using SirT3 (D22A3) Rabbit mAb (upper) and AIF (D39D2) XP® Rabbit mAb #5318 (lower).

Background

The Silent Information Regulator (SIR2) family of genes is a highly conserved group of genes that encode nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases, also known as Class III histone deacetylases. The first discovered and best characterized of these genes is Saccharomyces cerevisiae Sir2, which is involved in silencing of mating type loci, telomere maintenance, DNA damage response and cell aging (1). SirT3, a mammalian homolog of Sir2, exists in human cells in two forms. The full-length 44 kDa protein localizes to the nucleus, while a processed 28 kDa protein lacking 142 amino terminal residues localizes exclusively to the mitochondria (2-4). The single murine form of SirT3 is equivalent to the processed human SirT3 protein (2). Full-length SirT3 protein is processed in the mitochondrial matrix by the mitochondrial matrix processing peptidase (MMP) (3). Both full-length and processed forms of SirT3 are enzymatically active and de-acetylate histone H3 at Lys9 and histone H4 at Lys16 in vitro (2). SirT3 also de-acetylates Lys642 of acetyl-CoA synthetase 2 (AceCS2) and activates AceCS2 activity in the mitochondria (5). Restricted caloric intake, which is linked to increased lifespan in multiple organisms, increases SirT3 expression in white and brown adipocytes of obese mice, suggesting a role for SirT3 in aging (6). Two observations implicate SirT3 in the regulation of mitochondrial thermogenesis. First, exposure to cold temperatures increases SirT3 expression in brown adipocytes, while elevated temperatures reduce SirT3 expression (6). Second, over-expression of SirT3 results in increased levels of the mitochondrial uncoupling protein 1 (UCP1) (6). SirT3 protein levels are also elevated in certain breast cancers (7).

  1. Guarente, L. (1999) Nat Genet 23, 281-5.
  2. Scher, M.B. et al. (2007) Genes Dev 21, 920-8.
  3. Schwer, B. et al. (2002) J Cell Biol 158, 647-57.
  4. Onyango, P. et al. (2002) Proc Natl Acad Sci USA 99, 13653-8.
  5. Schwer, B. et al. (2006) Proc Natl Acad Sci USA 103, 10224-9.
  6. Shi, T. et al. (2005) J Biol Chem 280, 13560-7.
  7. Ashraf, N. et al. (2006) Br J Cancer 95, 1056-61.

Application References

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For Research Use Only. Not For Use In Diagnostic Procedures.

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