Table 1.
The identified substrates of sirtuins.
| Sirtuin | Known substrates | Process involved | Ref. |
|---|---|---|---|
| SIRT1 | ACSS1: K661 | Conversion of acetate to acetyl-CoA | [169] |
| AR: K630 | Androgen receptor signaling | [170] | |
| BMAL1: K537 | Circadian rhythms | [23] | |
| β-catenin | Suppression of tumorigenesis | [171] | |
| Cortactin | Cell migration | [172] | |
| CREB: K136 | Glucose and lipid metabolism | [81] | |
| CRTC2: K628 | Gluconeogenesis | [87] | |
| DNMT1: K1349, 1415 | DNA methylation | [173] | |
| eNOS: K496, K506 | Endothelium vasodilation | [174] | |
| FOXO1: K242, K245, K262, K274, K294, K559 | Transcription, autophagy, among others | [175–177] | |
| FOXO3: K242, K245, K259, K271, K290, K569 | Transcription | [177,178] | |
| FOXO4: K186, K189, K215, K237, K407 | Transcription | [177] | |
| Histone H1: K26 | Heterochromatin formation | [179] | |
| H2A.x | DNA damage response | [180] | |
| H2A.z: K15 | Cardiac hypertrophy | [181] | |
| Histone H3: K9 | Chromatin remodeling | [179] | |
| Histone H3: K56 | Chromatin remodeling | [182] | |
| Histone H4: K16 | Chromatin remodeling | [179] | |
| HIV Tat: K50 | HIV transcription | [183] | |
| HNF4α | Transcription | [184] | |
| Ku70: K539, K542 | DNA repair | [148] | |
| LKB1: K48 | Cell proliferation and metabolism | [130] | |
| LXRα: K432 | Lipid metabolism | [97] | |
| c-Myc: K323 | Cell proliferation | [185] | |
| MyoD: K99, K102, K104 | Muscle differentiation | [186] | |
| p53: K317, K370, K382 | Cell survival and stress response | [187,188] | |
| p300: K102, K1024 | Protein acetylation | [189] | |
| PARP1 | Cell survival | [190] | |
| PCAF | DNA damage response | [186] | |
| PER2 | Circadian rhythms | [22] | |
| PGC-1α: K77, K144, K183, K253, K270, K277, K320, K412, K441, K450, K757, K778 | Mitochondrial biogenesis and metabolism | [84] | |
| PGC-1β | Glucose and lipid metabolism | [191] | |
| NF-κBRelA/p65: K310 | Transcription | [192] | |
| Rb: K873, 874 | Cell cycle control | [193] | |
| Smad7: K64, K70 | Apoptosis | [194] | |
| SREBP-1c: K289, K309 | Lipid metabolism | [95] | |
| SUV39H1: K266 | Heterochromatin formation | [195] | |
| TAF(I)68 | rDNA transcription | [196] | |
| Zyxin | Cytoskeletal dynamics | [197] | |
| SIRT2 | CDC20 | Mitosis | [31] |
| CDH1 | Mitosis | [31] | |
| FOXO1: K262, K265, K274 | Adipogenesis and autophagy | [33,35] | |
| FOXO3: K242, K259, K290, K569 | Oxidative stress and ubiquitination | [30,116] | |
| Histone H3: K56 | DNA damage response | [198] | |
| Histone H4: K16 | Mitosis | [3] | |
| NF-κBRelA/p65: K310 | Transcription | [34] | |
| p53 | Cell survival and stress response | [199] | |
| p300: K418, K423, K1542, K1546, K1549, K1699, K1704, K1707 | Chromatin remodeling | [200] | |
| Par3: K831, K848, K881, K1327 | Myelination | [201] | |
| PEPCK: K70, K71, K594 | Gluconeogenesis | [32] | |
| PRLR | Prolactin receptor dimerization | [202] | |
| α-tubulin: K40 | Mitosis | [36] | |
| SIRT3 | ACSS2: K635 | Conversion of acetate to acetyl-CoA | [169,203] |
| ALDH2: K377 | Alcohol metabolism | [38] | |
| CYPD: K166 | Mitochondrial PTP control | [204] | |
| GDH | Glutamate oxidation and insulin secretion | [56] | |
| HMGCS2: K310, K447, K473 | Ketogenesis | [50] | |
| IDH2 | Anti-oxidative stress | [48] | |
| LCAD: K42 | Fatty acid oxidation | [53] | |
| MRPL10: K124, K162, K196 | Mitochondrial protein synthesis | [47] | |
| NDUF9A | Mitochondrial ETC | [54] | |
| OTC: K88 | Urea cycle | [43] | |
| SDH | Mitochondrial ETC | [205] | |
| SOD2: K53, K68, K89, K122 | Anti-oxidative stress | [51] | |
| SIRT4 | GDH | Glutamate oxidation and insulin secretion | [8,9] |
| SIRT5 | CPS1 | Urea cycle | [59] |
| CS | Citric acid cycle | [11] | |
| GDH | Amino acid-induced insulin secretion | [11] | |
| GOT2 | Amino acid metabolism | [11] | |
| HMGCS2 | Ketogenesis | [11] | |
| MDH | Citric acid cycle | [11] | |
| TST | Cyanide detoxification | [11] | |
| SIRT6 | CtIP: K432, K526, K604 | DNA repair | [66] |
| H3K9 | Chromatin remodeling | [69] | |
| H3K56 | Chromatin remodeling | [67,206] | |
| PARP1: K521 (mono-ADP-ribosylation) | DNA repair | [60] | |
| SIRT7 | p53 | Cell survival | [72] |
ETC: Electron transport chain; PTP: Permeability transition pore; Rb: Retinoblastoma.