Table 2.
Summary of Mechanisms of HbF production in response to hydroxyurea
| Signal level | Pathway | Mechanism of γ-globin induction | References |
|---|---|---|---|
| Epigenetic & Transcriptional Events | DNA remodelling DNA methylation |
Mi-2/NuRD; Acetylation and methylation DNMT-1 | [31,38,84,133,134] [131, 132] |
|
| |||
| Signalling pathways | Giα/JNK/Jun | NFκB induction of SAR1 | [82] |
|
| |||
| cGMP | sGC-PKG and NO-induced sGC-PKG | [86,88,90,91] | |
|
| |||
| cAMP | MYB transcriptional control | [90,124,135] | |
|
| |||
| MAPKs | Erk1-2/p38/JNK/CREB1 | [91,97–100,136] | |
|
| |||
| Nitric oxide | eNOS, flow-induced ATP and anti-sickling | [85,123] | |
|
| |||
| Phosphorylation | ElF2α | [128] | |
|
| |||
| Transcription factors | GATA-1/2; p21; EPO; KLF1 | [32,101,137] | |
|
| |||
| Stress signals | ROS (superoxide and hydroxyl radicals) | [104] | |
|
| |||
| Post-transcription | Translational Regulation | miR-494; 15a; 16-1; 151-3p; 148b | [84,124–126,138–141] |