Human Gene SIRT1 (uc001jnd.3) Description and Page Index
Description: Homo sapiens sirtuin 1 (SIRT1), transcript variant 1, mRNA. RefSeq Summary (NM_012238): This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]. Transcript (Including UTRs) Position: hg19 chr10:69,644,427-69,678,147 Size: 33,721 Total Exon Count: 9 Strand: + Coding Region Position: hg19 chr10:69,644,480-69,676,350 Size: 31,871 Coding Exon Count: 9
ID:SIR1_HUMAN DESCRIPTION: RecName: Full=NAD-dependent protein deacetylase sirtuin-1; Short=hSIRT1; EC=3.5.1.-; AltName: Full=Regulatory protein SIR2 homolog 1; AltName: Full=SIR2-like protein 1; Short=hSIR2; Contains: RecName: Full=SirtT1 75 kDa fragment; Short=75SirT1; FUNCTION: NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of 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. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A- mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insuline-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. 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 probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys- 542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in 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. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys- 70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transacivation and contributes to its stability. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection. FUNCTION: SirtT1 75 kDa fragment: catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly. CATALYTIC ACTIVITY: NAD(+) + an acetylprotein = nicotinamide + O- acetyl-ADP-ribose + a protein. COFACTOR: Binds 1 zinc ion per subunit (By similarity). ENZYME REGULATION: Inhibited by nicotinamide. Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'- tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans- stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'- pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity. Negatively regulated by KIAA1967/DBC1. SUBUNIT: Found in a complex with PCAF and MYOD1. Interacts with FOXO1; the interaction deacetylates FOXO1, resulting in its nuclear retention and promotion of its transcriptional activity Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with KIAA1967/DBC1 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with HIV-1 tat. INTERACTION: Q13085:ACACA; NbExp=3; IntAct=EBI-1802965, EBI-717681; P31749:AKT1; NbExp=5; IntAct=EBI-1802965, EBI-296087; P27695:APEX1; NbExp=6; IntAct=EBI-1802965, EBI-1048805; P33076:CIITA; NbExp=4; IntAct=EBI-1802965, EBI-1538819; Q9NS37:CREBZF; NbExp=3; IntAct=EBI-1802965, EBI-632965; P68400:CSNK2A1; NbExp=2; IntAct=EBI-1802965, EBI-347804; P26358:DNMT1; NbExp=11; IntAct=EBI-1802965, EBI-719459; Q01094:E2F1; NbExp=3; IntAct=EBI-1802965, EBI-448924; Q09472:EP300; NbExp=2; IntAct=EBI-1802965, EBI-447295; Q14192:FHL2; NbExp=2; IntAct=EBI-1802965, EBI-701903; Q12778:FOXO1; NbExp=3; IntAct=EBI-1802965, EBI-1108782; Q9R1E0:Foxo1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-1371343; O43524:FOXO3; NbExp=5; IntAct=EBI-1802965, EBI-1644164; P98177:FOXO4; NbExp=3; IntAct=EBI-1802965, EBI-4481939; P51610:HCFC1; NbExp=2; IntAct=EBI-1802965, EBI-396176; Q14469:HES1; NbExp=4; IntAct=EBI-1802965, EBI-2832522; Q9UBP5:HEY2; NbExp=3; IntAct=EBI-1802965, EBI-750630; Q9Y4H2:IRS2; NbExp=2; IntAct=EBI-1802965, EBI-1049582; Q92831:KAT2B; NbExp=3; IntAct=EBI-1802965, EBI-477430; Q8N163:KIAA1967; NbExp=9; IntAct=EBI-1802965, EBI-355410; Q03112:MECOM; NbExp=2; IntAct=EBI-1802965, EBI-1384862; P42345:MTOR; NbExp=2; IntAct=EBI-1802965, EBI-359260; P01106:MYC; NbExp=4; IntAct=EBI-1802965, EBI-447544; P04198:MYCN; NbExp=3; IntAct=EBI-1802965, EBI-878369; O60934:NBN; NbExp=5; IntAct=EBI-1802965, EBI-494844; Q60974:Ncor1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-349004; Q02577:NHLH2; NbExp=2; IntAct=EBI-1802965, EBI-5378683; Q9HAN9:NMNAT1; NbExp=3; IntAct=EBI-1802965, EBI-3917542; Q15466:NR0B2; NbExp=6; IntAct=EBI-1802965, EBI-3910729; Q60644:Nr1h2 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276809; Q9Z0Y9:Nr1h3 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276764; P27986:PIK3R1; NbExp=3; IntAct=EBI-1802965, EBI-79464; P10276:RARA; NbExp=3; IntAct=EBI-1802965, EBI-413374; Q04206:RELA; NbExp=4; IntAct=EBI-1802965, EBI-73886; Q86WX3:RPS19BP1; NbExp=9; IntAct=EBI-1802965, EBI-4479407; Q8N122:RPTOR; NbExp=3; IntAct=EBI-1802965, EBI-1567928; O43159:RRP8; NbExp=3; IntAct=EBI-1802965, EBI-2008793; Q13573:SNW1; NbExp=7; IntAct=EBI-1802965, EBI-632715; P36956-3:SREBF1; NbExp=2; IntAct=EBI-1802965, EBI-948338; O54864:Suv39h1 (xeno); NbExp=4; IntAct=EBI-1802965, EBI-302230; P04608:tat (xeno); NbExp=3; IntAct=EBI-1802965, EBI-6164389; Q04724:TLE1; NbExp=4; IntAct=EBI-1802965, EBI-711424; P04637:TP53; NbExp=13; IntAct=EBI-1802965, EBI-366083; O15350:TP73; NbExp=4; IntAct=EBI-1802965, EBI-389606; P49815:TSC2; NbExp=2; IntAct=EBI-1802965, EBI-396587; Q14191:WRN; NbExp=9; IntAct=EBI-1802965, EBI-368417; P23025:XPA; NbExp=8; IntAct=EBI-1802965, EBI-295222; P12956:XRCC6; NbExp=7; IntAct=EBI-1802965, EBI-353208; SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm. Note=Recruited to the nuclear bodies via its interaction with PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus, nuclear euchromatin, heterochromatin and inner membrane. Shuttles between nucleus and cytoplasm. SUBCELLULAR LOCATION: SirtT1 75 kDa fragment: Cytoplasm. Mitochondrion. TISSUE SPECIFICITY: Widely expressed. INDUCTION: Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum. PTM: Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53. PTM: 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 acivates 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. PTM: Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1). PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity (By similarity). MISCELLANEOUS: Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as it has been observed in yeast. MISCELLANEOUS: Calf histone H1 is used as substrate in the in vitro deacetylation assay (PubMed:15469825). As, in vivo, interaction occurs between SIRT1 with HIST1H1E, deacetylation has been validated only for HIST1H1E. MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant (PubMed:19220062). SIMILARITY: Belongs to the sirtuin family. Class I subfamily. SIMILARITY: Contains 1 deacetylase sirtuin-type domain. SEQUENCE CAUTION: Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/sirt1/";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): SIRT1 CDC HuGE Published Literature: SIRT1
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96EB6
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000012 single strand break repair GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000183 chromatin silencing at rDNA GO:0000720 pyrimidine dimer repair by nucleotide-excision repair GO:0000731 DNA synthesis involved in DNA repair GO:0001525 angiogenesis GO:0001542 ovulation from ovarian follicle GO:0001678 cellular glucose homeostasis GO:0001934 positive regulation of protein phosphorylation GO:0001938 positive regulation of endothelial cell proliferation GO:0002821 positive regulation of adaptive immune response GO:0006325 chromatin organization GO:0006342 chromatin silencing GO:0006343 establishment of chromatin silencing GO:0006344 maintenance of chromatin silencing GO:0006346 methylation-dependent chromatin silencing GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006364 rRNA processing GO:0006366 transcription from RNA polymerase II promoter GO:0006476 protein deacetylation GO:0006642 triglyceride mobilization GO:0006915 apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0006979 response to oxidative stress GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007275 multicellular organism development GO:0007283 spermatogenesis GO:0007346 regulation of mitotic cell cycle GO:0007517 muscle organ development GO:0007569 cell aging GO:0007623 circadian rhythm GO:0008284 positive regulation of cell proliferation GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0009267 cellular response to starvation GO:0010629 negative regulation of gene expression GO:0010875 positive regulation of cholesterol efflux GO:0010883 regulation of lipid storage GO:0010906 regulation of glucose metabolic process GO:0010934 macrophage cytokine production GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0016032 viral process GO:0016239 positive regulation of macroautophagy GO:0016567 protein ubiquitination GO:0016575 histone deacetylation GO:0018394 peptidyl-lysine acetylation GO:0030154 cell differentiation GO:0030225 macrophage differentiation GO:0030308 negative regulation of cell growth GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway GO:0031393 negative regulation of prostaglandin biosynthetic process GO:0031648 protein destabilization GO:0031937 positive regulation of chromatin silencing GO:0032007 negative regulation of TOR signaling GO:0032071 regulation of endodeoxyribonuclease activity GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032868 response to insulin GO:0032922 circadian regulation of gene expression GO:0033158 regulation of protein import into nucleus, translocation GO:0033210 leptin-mediated signaling pathway GO:0034391 regulation of smooth muscle cell apoptotic process GO:0034983 peptidyl-lysine deacetylation GO:0035356 cellular triglyceride homeostasis GO:0035358 regulation of peroxisome proliferator activated receptor signaling pathway GO:0042127 regulation of cell proliferation GO:0042326 negative regulation of phosphorylation GO:0042542 response to hydrogen peroxide GO:0042595 behavioral response to starvation GO:0042632 cholesterol homeostasis GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042981 regulation of apoptotic process GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator GO:0043536 positive regulation of blood vessel endothelial cell migration GO:0044321 response to leptin GO:0045348 positive regulation of MHC class II biosynthetic process GO:0045599 negative regulation of fat cell differentiation GO:0045739 positive regulation of DNA repair GO:0045766 positive regulation of angiogenesis GO:0045892 negative regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046628 positive regulation of insulin receptor signaling pathway GO:0048511 rhythmic process GO:0050872 white fat cell differentiation GO:0051097 negative regulation of helicase activity GO:0051152 positive regulation of smooth muscle cell differentiation GO:0051574 positive regulation of histone H3-K9 methylation GO:0051898 negative regulation of protein kinase B signaling GO:0055089 fatty acid homeostasis GO:0060766 negative regulation of androgen receptor signaling pathway GO:0061647 histone H3-K9 modification GO:0070301 cellular response to hydrogen peroxide GO:0070857 regulation of bile acid biosynthetic process GO:0070914 UV-damage excision repair GO:0070932 histone H3 deacetylation GO:0071356 cellular response to tumor necrosis factor GO:0071441 negative regulation of histone H3-K14 acetylation GO:0071456 cellular response to hypoxia GO:0071479 cellular response to ionizing radiation GO:0071900 regulation of protein serine/threonine kinase activity GO:0090335 regulation of brown fat cell differentiation GO:0090400 stress-induced premature senescence GO:1900034 regulation of cellular response to heat GO:1900113 negative regulation of histone H3-K9 trimethylation GO:1901215 negative regulation of neuron death GO:1901984 negative regulation of protein acetylation GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1904179 positive regulation of adipose tissue development GO:1990619 histone H3-K9 deacetylation GO:1990830 cellular response to leukemia inhibitory factor GO:2000111 positive regulation of macrophage apoptotic process GO:2000480 negative regulation of cAMP-dependent protein kinase activity GO:2000481 positive regulation of cAMP-dependent protein kinase activity GO:2000619 negative regulation of histone H4-K16 acetylation GO:2000655 negative regulation of cellular response to testosterone stimulus GO:2000757 negative regulation of peptidyl-lysine acetylation GO:2000773 negative regulation of cellular senescence GO:2000774 positive regulation of cellular senescence GO:0006471 protein ADP-ribosylation