Table 4.
List of substrates specifically deacetylated by HDAC6.
| Substrates | Localization of the Substrate | Deacetylated Lysine(s) | Function of the Deacetylated Substrate | Interaction Domains of HDAC6 | Reference |
|---|---|---|---|---|---|
| 14-3-3ζ | Cytoplasm and nucleus | 49, 120 | Regulation of protein binding Bad and AS160 | ND | [85] |
| β-catenin | Cytoplasm and nucleus | 49 | Epidermal growth factor-induced nuclear localization and decreased expression of c-Myc | ND | [83] |
| Cortactin * | Cytoplasm | 87, 124, 161, 189, 198, 235, 272, 309, 319 | Regulation of cell migration and actin filament binding | DD1 and DD2 | [83] |
| DNAJA1 | Cytoplasm | ND | Protein folding | ND | [86] |
| ERK1 | Cytoplasm and nucleus | 72 | Proliferation, mobility, and cell survival | [87] | |
| Foxp3 * | Nucleus | ND | ND | ND | [88] |
| HDAC9 | Cytoplasm and nucleus | ND | Modulation of cell survival and arrest of cellular movement | DD2 | [89] |
| HDAC11 | Nucleus | ND | Transcriptional activation of interleukin 10 | ND | [90] |
| HMGN2 | Nucleus | 2 | Increased transcription of STAT5 | ND | [91] |
| HSC70 | Cytoplasm | ND | Protein folding | ND | [86] |
| HSPA5 | Cytoplasm | 353 | Ubiquitination of HSPA5 mediated by GP78 | ND | [92] |
| HSP90α | Cytoplasm | 294 | Degradation and elimination of misfolded proteins and regulation of glucocorticoid receptors | DD1, DD2 et BUZ | [83] |
| K-RAS * | Cytoplasm | 104 | Cell proliferation | ND | [93] |
| Ku70 | Cytoplasm | 539, 542 | Suppression of apoptosis | ND | [83] |
| LC3B-II* | Cytoplasm | ND | Regulation of autophagy | ND | [94] |
| MSH2 | Cytoplasm and nucleus | 845, 847, 871, 892 | Reduced cellular sensitivity to DNA damaging agents and reduced DNA mismatch repair activities by downregulation of MSH2 | DD1 | [95] |
| MYH9 | Cytoplasm | ND | Regulation of binding to actin filaments | ND | [86] |
| PrxI | Cytoplasm and nucleus | 197 | Antioxidant activity | ND | [96,97] |
| PrxII | Cytoplasm and nucleus | 196 | Antioxidant activity | ND | [96,97] |
| RIG-I | Cytoplasm | 858, 909 | Recognition of viral RNA | ND | [98] |
| Sam68 | Nucleus | ND | Alternative splicing | ND | [99] |
| Survivin | Nucleus | 129 | Anti-apoptotic function | DD2 | [83] |
| Tat | Cytoplasm | 28 | Suppression of HIV transactivation | DD2 and BUZ | [100] |
| α-tubulin * | Cytoplasm | 40 | Formation of immune synapses, viral infection, cell migration and chemotaxis | DD1 or DD2 | [83,101] |
* Cortactin and LC3B-II are also deacetylated by SIRT1, K-RAS and α-tubulin are also deacetylated by SIRT2, and Foxp3 is also deacetylated by HDAC9 and SIRT1. AS160: Akt substrate of 160 kDa; Bad: Bcl-2 associated agonist of cell death; BUZ: binding-of-ubiquitin zinc; DD: deacetylase domain; DNAJA1: dnaJ homolog subfamily A member 1; ERK1: extracellular signal-regulated kinase 1; Foxp3: forkhead box P3; GP: glycoprotein; HDAC: histone deacetylase; HIV: human immunodeficiency virus; HMGN2: high mobility group nucleosomal binding domain 2; HSC: heat shock cognate; HSP (A): heat shock protein [family A (HSP70) member 5]; LC3B-II: microtubule-associated protein 1 light chain 3; MSH2: MutS protein homolog 2; MYH9: myosin heavy chain 9; ND: non determined; Prx: peroxiredoxin; RIG-I: retinoic acid-inducible gene I protein; Sam: Src-associated substrate in mitosis; STAT: signal transducer and transcriptional activator; Tat: twin-arginine translocation protein.