Trim39 acts as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3. Indeed, Trim39 preferentially binds and ubiquitinates the SUMOylated forms of NFATc3 by its SUMO interacting motifs (SIM), mostly its so-called SIM3. In the absence of Trim17 (black arrows), Trim39 ubiquitinates SUMOylated NFATc3, possibly on its SUMO chains or other sites. This induces the proteasomal degradation of NFATc3 and reduces the expression of its target genes, thereby promoting neuronal survival. In the presence of Trim17 (red arrows), Trim39-mediated ubiquitination and degradation of NFATc3 is inhibited, which stabilizes NFATc3 and increases the expression of its target genes, including Trim17 itself. This creates a positive feedback loop that favors neuronal apoptosis.
- Meenakshi Basu-Shrivastava
- Barbara Mojsa
- Solange Desagher
