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The group of Solange Desagher identified a novel STUbL in mammals.

Basu-Shrivastava et al. showed that Trim39 acts as a SUMO-targeted E3 ubiquitin-ligase (STUbL) for the transcription factor NFATc3 that regulates neuronal apoptosis. Indeed, Trim39 preferentially binds and ubiquitinates the SUMOylated forms of NFATc3 by its SUMO interacting motifs (SIM). In the absence of Trim17 (black arrows), Trim39 ubiquitinates SUMOylated NFATc3. 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.
Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3.
Basu-Shrivastava M, Mojsa B, Mora S, Robbins I, Bossis G, Lassot I, Desagher S. Cell Death Differ. 2022 Apr 21. doi: 10.1038/s41418-022-01002-2. Online ahead of print. PMID: 35449213