SIRT1 Antibody, HRP conjugated

75SirT1 antibody; hSIR2 antibody; hSIRT1 antibody; HST2 antibody; HST2, S. cerevisiae, homolog of antibody; NAD dependent deacetylase sirtuin 1 antibody; NAD dependent protein deacetylase sirtuin 1 antibody; NAD-dependent deacetylase sirtuin-1 antibody; OTTHUMP00000198111 antibody; OTTHUMP00000198112 antibody; Regulatory protein SIR2 homolog 1 antibody; SIR1_HUMAN antibody; SIR2 antibody; SIR2 like 1 antibody; SIR2 like protein 1 antibody; SIR2, S.cerevisiae, homolog-like 1 antibody; SIR2-like protein 1 antibody; SIR2ALPHA antibody; SIR2L1 antibody; Sirt1 antibody; SirtT1 75 kDa fragment antibody; Sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) antibody; Sirtuin 1 antibody; Sirtuin type 1 antibody

SIRT1, a NAD-dependent protein deacetylase, plays a pivotal role in linking transcriptional regulation to intracellular energy levels. It participates in coordinating various cellular functions, including cell cycle regulation, response to DNA damage, metabolic processes, apoptosis, and autophagy. SIRT1 modulates chromatin function by deacetylating histones, promoting alterations in histone and DNA methylation, and ultimately leading to transcriptional repression. It deacetylates a diverse range of transcription factors and coregulators, thereby regulating target gene expression in both positive and negative manners. SIRT1 acts as a sensor for the cytosolic NAD+/NADH ratio, which is influenced by glucose deprivation and metabolic changes associated with caloric restriction.

SIRT1 is essential for skeletal muscle cell differentiation. Under conditions of low nutrient availability, SIRT1 mediates the inhibitory effect on skeletal myoblast differentiation, a process that also involves the participation of 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). SIRT1 is a component of the eNoSC (energy-dependent nucleolar silencing) complex, which mediates the silencing of rDNA in response to intracellular energy status by recruiting histone-modifying enzymes. The eNoSC complex senses the energy status of the cell: upon glucose starvation, the elevation of the NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation, followed by dimethylation of H3 at Lys-9 (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. SIRT1 deacetylates Lys-266 of SUV39H1, leading to its activation.

SIRT1 inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. It deacetylates H2A and Lys-26 of H1-4. In vitro, SIRT1 deacetylates Lys-16 of histone H4. SIRT1 is involved in NR0B2/SHP corepression function through chromatin remodeling. It is recruited to LRH1 target gene promoters by NR0B2/SHP, stimulating histone H3 and H4 deacetylation, which leads to transcriptional repression. SIRT1 is proposed to contribute to genomic integrity through the positive regulation of telomere length; however, its localization to pericentromeric heterochromatin has been reported with conflicting results. SIRT1 is proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance by regulating the available pool of nuclear SUV39H1. Under oxidative/metabolic stress, SIRT1 reduces SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which, in turn, accelerates heterochromatin renewal. This renewal correlates with greater genomic integrity during stress response.

SIRT1 deacetylates Lys-382 of p53/TP53, impairing its ability to induce transcription-dependent proapoptotic programs and modulate cell senescence. It deacetylates TAF1B, repressing rDNA transcription by RNA polymerase I. SIRT1 deacetylates MYC, promoting the association of MYC with MAX and decreasing MYC stability, leading to compromised transformational capability. SIRT1 deacetylates FOXO3 in response to oxidative stress, increasing its ability to induce cell cycle arrest and resistance to oxidative stress while inhibiting FOXO3-mediated induction of apoptotic transcriptional activity. This deacetylation also leads to FOXO3 ubiquitination and proteasomal degradation. SIRT1 appears to have a similar effect on MLLT7/FOXO4 in regulating transcriptional activity and apoptosis. SIRT1 deacetylates DNMT1, impairing its methyltransferase-independent transcription repressor activity, modulating DNMT1 cell cycle regulatory function, and DNMT1-mediated gene silencing. SIRT1 deacetylates RELA/NF-kappa-B p65, inhibiting its transactivating potential and augmenting apoptosis in response to TNF-alpha. It deacetylates HIF1A, KAT5/TIP60, RB1, and HIC1.

SIRT1 deacetylates FOXO1, leading to its nuclear retention and enhancement of its transcriptional activity, resulting in increased gluconeogenesis in the liver. SIRT1 inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. SIRT1 is involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN, SIRT1 seems to be involved in transcriptional repression of DUSP6/MAPK3, leading to MYCN stabilization by phosphorylation at Ser-62. SIRT1 deacetylates MEF2D. It is required for antagonist-mediated transcription suppression of AR-dependent genes, which may be linked to local deacetylation of histone H3. SIRT1 represses HNF1A-mediated transcription. It is required for the repression of ESRRG by CREBZF. SIRT1 deacetylates NR1H3 and NR1H2. Deacetylation of NR1H3 at Lys-434 positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation, and results in cholesterol efflux. A promoter clearing mechanism after each round of transcription has been proposed.

SIRT1 is involved in lipid metabolism. It is implicated in the regulation of adipogenesis and fat mobilization in white adipocytes by repressing PPARG, which likely involves association with NCOR1 and SMRT/NCOR2. SIRT1 deacetylates p300/EP300 and PRMT1. It deacetylates ACSS2, leading to its activation, and HMGCS1 deacetylation. SIRT1 is involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A, SIRT1 is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis. SIRT1 is involved in the regulation of PPARA and fatty acid beta-oxidation in the liver. It is involved in the positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. SIRT1 is proposed to deacetylate IRS2, facilitating its insulin-induced tyrosine phosphorylation. SIRT1 deacetylates SREBF1 isoform SREBP-1C, decreasing its stability and transactivation in lipogenic gene expression.

SIRT1 is involved in the DNA damage response by repressing genes involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating the recruitment of additional factors to sites of damaged DNA. For example, SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair, and SIRT1-deacetylated XPA interacts with RPA2. SIRT1 is also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC likely involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 likely involves E2F4 and PCAF. SIRT1 deacetylates WRN, regulating its helicase and exonuclease activities and regulating WRN nuclear translocation in response to DNA damage. SIRT1 deacetylates APEX1 at Lys-6 and Lys-7, stimulating cellular AP endonuclease activity by promoting the association of APEX1 with XRCC1. SIRT1 increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and likely redirecting it to mitochondria. SIRT1 deacetylates XRCC6/Ku70 at Lys-539 and Lys-542, causing it to sequester BAX away from mitochondria, thereby inhibiting stress-induced apoptosis.

SIRT1 is involved in autophagy, presumably by deacetylating ATG5, ATG7, and MAP1LC3B/ATG8. SIRT1 deacetylates AKT1, leading to enhanced binding of AKT1 and PDK1 to PIP3 and promoting their activation. SIRT1 is proposed to play a role in the regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence, which seems to involve the regulation of the acetylation status of STK11/LBK1. SIRT1 can deacetylate STK11/LBK1, increasing its activity, cytoplasmic localization, and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells, SIRT1 inhibits STK11/LBK1 activity and promotes its degradation. SIRT1 deacetylates SMAD7 at Lys-64 and Lys-70, promoting its degradation. SIRT1 deacetylates CIITA, augmenting its MHC class II transactivation and contributing to its stability. SIRT1 deacetylates MECOM/EVI1. SIRT1 deacetylates PML at Lys-487, and this deacetylation promotes PML control of PER2 nuclear localization.

During the neurogenic transition, SIRT1 represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner, leading to neuronal differentiation. SIRT1 regulates the circadian expression of several core clock genes, including ARNTL/BMAL1, RORC, PER2, and CRY1, and plays a critical role in maintaining controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. SIRT1 deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters to facilitate repression by inhibitory components of the circadian oscillator. SIRT1 deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome. SIRT1 protects cardiomyocytes against palmitate-induced apoptosis. SIRT1 deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity. SIRT1 deacetylates PCK1 and directs its activity towards phosphoenolpyruvate production, promoting gluconeogenesis. SIRT1 is involved in the CCAR2-mediated regulation of PCK1 and NR1D1. SIRT1 deacetylates CTNB1 at Lys-49. In POMC (pro-opiomelanocortin) neurons, SIRT1 is required for leptin-induced activation of PI3K signaling.

In addition to protein deacetylase activity, SIRT1 also acts as a protein-lysine deacylase. It acts as a protein depropionylase by mediating depropionylation of Osterix (SP7). SIRT1 deacetylates SOX9, promoting SOX9 nuclear localization and transactivation activity. SIRT1 is involved in the regulation of centrosome duplication. It deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly.

[Isoform 2]: SIRT1 isoform 2 deacetylates Lys-382 of p53/TP53, although with lower activity than isoform 1. The two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response. It is, in turn, repressed by p53/TP53, presenting a SIRT1 isoform-dependent auto-regulatory loop.

(Microbial infection) In the case of HIV-1 infection, SIRT1 interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity towards RELA/NF-kappa-B p65, thereby potentiating its transcriptional activity. SIRT1 is proposed to contribute to T-cell hyperactivation during infection.

[SirtT1 75 kDa fragment]: The catalytically inactive 75SirT1 may be involved in regulating apoptosis. It may be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly.