Table 1.
Post-translational modifications described for HSF1
| PTM | Enzyme | Effect | Physiological context | Refs |
|---|---|---|---|---|
| Phosphorylation | ||||
| Ser121 | MK2, AMPK | HSP90 binding and repression | Cancer (↓), metabolic stress (↑) | 41,126,127 |
| Ser127 | – | – | 128 | |
| Thr142 | CK2 | DNA binding activation | Heat shock (↑) | 129 |
| Ser195 | – | LZ1–3 and LZ4 dissociation and transactivation | Heat shock (↑) | 130 |
| Ser216 | PLK1 | Protein degradation, mitotic progression | Mitosis (↑) | 25 |
| Ser230 | CaMKII | Activation | Heat shock (↑) | 126,131 |
| Ser292 | – | – | 39,126 | |
| Ser303 | GSK3β, ERK1, MEK1, CK2 | Attenuation and degradation | Cancer (↓), HD (↑) | 3,40,126,128, 132 134 |
| Ser307 | GSK3β, ERK1, MEK1, CK2 | Attenuation and degradation | Cancer (↓), HD (↑) | 3,40,126 128 |
| Ser314 | – | – | Cancer (↓) | 126,127 |
| Ser319 | – | – | – | 126 |
| Ser320 | PKAcα | Activation | Heat shock (↑) | 135 |
| Thr323 | – | Repression | Heat shock (↑) | 127 |
| Ser326 | mTOR, ERK1/2, MEK1 | Activation | Heat shock (↑), cancer (↓) | 106,126,136 |
| Ser333 | PKCθ | HSP90 dissociation and activation | Cancer (↑) | 137 |
| Ser344 | – | – | 126 | |
| Ser363 | PKCα, PKCζ, JNK | Repression | Heat shock (↓) | 126,128,134 |
| Thr367 | – | Repression | Cancer (↓) | 127 |
| Ser419 | PLK1 | Nuclear localization and activation | Heat shock (↓) | 126 |
| Ser444 | – | – | 126 | |
| Acetylation | ||||
| Lys80 | GCN5, p300 | Inhibition, DNA binding dissociation | Heat shock (↓) | 31,37,38 |
| SIRT1, HDAC7, HDAC9 | ||||
| Lys116 | – | – | 31 | |
| Lys118 | p300 | Inhibition | Heat shock (↑) | 31,32 |
| Lys126, Lys148 | – | – | 31 | |
| Lys157, Lys188 | – | – | 31,138 | |
| Lys208 | p300 | Protein stabilization | Basal conditions (↑) | 31,32 |
| Lys224 | – | – | 31 | |
| Lys298 | p300 | Protein stabilization | Basal conditions (↑) | 31,32 |
| Lys524 | – | Heat shock response | Heat shock (↑) | 32 |
| Sumoylation | ||||
| Lys62, Lys91, Lys116, Lys118, Lys126, Lys131, Lys139, Lys148, Lys157, Lys162, Lys184, Lys208 | – | – | 43 | |
| Lys298 | UBC9 | Repression | Heat shock (↓) | 43,132 |
| Lys372 | – | – | 43 | |
Arrows indicate stress and/or pathological conditions in which alterations in particular modifications have been reported. ‘–’ indicates that the function of this post-translational modification is not known or has not been assessed yet. AMPK, 5′-AMP-activated protein kinase; CaMKII, calcium/calmodulin-dependent protein kinase type II; CK2, casein kinase 2; ERK1, extracellular signal-regulated kinase; GSK3β, glycogen synthase kinase 3β; HD, Huntington disease; HDAC, histone deacetylase; HSF1, heat shock factor 1; HSP90, heat shock protein 90; JNK, JUN N-terminal kinase; LZ, leucine zipper; MEK1 (mitogen-activated protein kinase kinase 1; MK2, MAP kinase-activated protein kinase 2; mTOR, mechanistic target of rapamycin; PKAcα, cAMP-dependent protein kinase catalytic subunit; PKC, protein kinase C; PLK1, polo-like kinase 1; SIRT1, NAD-dependent protein deacetylase sirtuin 1.