Table 1.
Posttranslational modifications of STAT3.
| Residue | Domain | Modification | Function |
|---|---|---|---|
| R31 | NTD | Methylation | • Attenuation of activation (27) |
| K49 | NTD | Dimethylation | • Increased gene expression (28) |
| K49, K87 | NTD | Acetylation | • Stable p300 association and gene expression (29, 30) |
| • HDAC1 association and nuclear export (termination of transcription) (31) | |||
| K87 | NTD | Acetylation | • Sin3a-mediated transcription repression (32) |
| K97 | NTD | Mono-ubiquitination | • Anti-apoptotic (BRD4-dependent) gene expression (33) |
| K140 | CCD | Dimethylation | • Decreased gene expression (34) |
| K180 | CCD | Trimethylation | • Increased Y505 phosphorylation/gene expression (35) |
| C259 | CCD | S-nitrosylation | • Inhibits Y705 activation (phosphorylation) (36) |
| K685, K707, K709 | SH2, TAD, TAD | Acetylation | • Regulation of Y705 phosphorylation (37) |
| • Inhibition of gluconeogenesis genes in liver (37) | |||
| K685 | SH2 | Acetylation | • Stable dimer formation, DNA binding, transcription (38, 39) |
| • Interaction with DNMT1 and gene silencing (40, 41) | |||
| • U-STAT3-mediated gene expression (42) | |||
| Y705 | TAD | Phosphorylationa | • Enhances dimerization and transcription/gene expression (1) |
| T714, S727 | TAD | Phosphorylation | • Gene expression (43) |
| S727 | TAD | Phosphorylationa | • Enhances gene expression (44) |
| • Mitochondrial actions (1, 4, 5, 45–48) | |||
| • Recruitment of tyrosine phosphatases/transcription termination (1, 49, 50) |
CCD, coiled coil domain; NTD, N terminus domain; SH2, Src homology 2 domain; TAD, transcription activation domain. aDemonstrated in cardiac myocytes.