EC Number   |
General Information |
Reference |
|---|
   2.3.1.B41 | malfunction |
an inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality. The homozygous inactivating mutation D63H in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses. Human induced pluripotent stem cells (iPSCs) derived from D63H homozygous fetuses fail to differentiate into embryoid bodies (EBs), functional cardiomyocytes, and neural progenitor cells due to a failure to repress pluripotent genes. SIRT6 knockout ESCs cultured to form EBs are significantly smaller than their wild-type counterparts. SIRT6 D63H mutant mESCs fail to differentiate into functional cardiomyocyte foci. SIRT6 D63H mutant cardiomyocytes fail to suppress HAND1 expression while exhibiting significantly reduced FBN1 levels when compared with SIRT6 knockout cells |
756879 |
| 2.3.1.B41 | malfunction |
analysis of effects of inhibition of SIRT6 on differentiation and lipid synthesis, and related molecular mechanisms, overview. Overexpression of SIRT6 significantly inhibits the mRNA expression of key adipogenesis genes such as CCAAT enhancer binding protein alpha (CEBPalpha), FABP4, FASN, peroxisome proliferator-activated receptor gamma (PPARgamma), and stearoyl-CoA desaturase (SCD), and promotes the expression of lipolysis genes including lipoprotein lipase (LPL), while interference of SIRT6 obtains the opposite results. The lipolysis drug Cl316,243 interfering with SIRT6 significantly promotes the expression of CEBPalpha, FABP4, FASN, PPARgamma, and SCD, and inhibited the expression of LPL, while overexpression of SIRT6 results in the opposite results |
755904 |
| 2.3.1.B41 | metabolism |
cells overexpressing Sirt6 have a lower proliferation rate with a lower percentage of cells in mitosis, roles for Sirt6 in the nucleolus and in the mitotic phase of the cell cycle |
730527 |
| 2.3.1.B41 | metabolism |
circadian clock relies on a transcription and translation feedback loop (TTFL). Two transcription factors, i.e. Bmal1 and Clock, activate the transcription of Period (Per) and Cryptochrome (Cry), which inhibit their own transcription when accumulated to a critical concentration. NAD+-dependent deacylase Sirt1 deacetylates Bmal1 and Per2 to regulate circadian rhythms. Sirt6 interacts with Bmal1 to regulate clock-controlled gene (CCG) expression by local chromatin remodeling. Loss of Sirt6 jeopardizes circadian phase. At molecular level, Sirt6 interacts with and deacetylates Per2, thus preventing its proteasomal degradation. Important function of Sirt6 in the direct regulation of TTFL and circadian rhythms |
755978 |
| 2.3.1.B41 | malfunction |
diabetic mice exhibit reduced Sirt6 expression and AMP kinase (AMPK) dephosphorylation accompanied by mitochondrial morphological abnormalities. Hyperglycemia-induced Sirt6 levels are decreased in vivo. Hyperglycemia promotes podocyte mitochondrial dysfunction in mice with diabetic nephropathy (DN) |
-, 756973 |
| 2.3.1.B41 | malfunction |
downregulation of SIRT6 enables forkhead box O3 (FOXO3) upregulation, translocation into the nucleus, and increased expression of its target genes p27 and Bim, which further induce apoptosis. Overexpression of SIRT6, but not enzyme-inactivated mutants, prevents FOXO3 translocation into the nucleus and doxorubicin-induced cell death |
757883 |
| 2.3.1.B41 | malfunction |
E-cadherin degradation and invasion, migration induced by SIRT6 overexpression can be rescued by dual mutation of Beclin-1 (inhibition of acetylation), CQ (autophagy inhibitor), and knockdown of Atg7 |
757530 |
| 2.3.1.B41 | malfunction |
enzyme inactivation in cells leads to histone H3-Lys18 hyperacetylation and aberrant accumulation of pericentric transcripts |
739158 |
| 2.3.1.B41 | malfunction |
enzyme knockout is associated with derepression of Oct4, Sox2 and Nanog, which in turn causes an upregulation of Tet enzymes and elevated production of 5-hydroxymethylcytosine |
739132 |
| 2.3.1.B41 | physiological function |
enzyme overexpression inhibits the proliferation of ovarian cancer cells SKOV-3 and OVCAR-3. The enzyme suppresses the expression of Notch 3 both at the mRNA and protein levels in ovarian cancer cells |
738169 |
