Proteasomal degradation of AMOT as a mechanotrasduction rheostat

Mechanotransduction is the process through which cells translate external mechanical cues into specific transcriptional programs (Discher et al., 2009; Ferrai & Schulte 2024). Cells translate external mechanical stimulations into internal tensional forces, through the re-arrangement of the F-actin cytoskeleton (Aragona et al., 2013). Downstream of these events, YAP and TAZ transcriptional co-activators translocate into the nucleus, where they interact with TEAD transcription factors to initiate specific transcriptional programs (Dupont et al., 2011; Battilana et al., 2021). Yet, despite extensive efforts, the precise biochemical events that translate mechanical events into YAP/TAZ nuclear translocation remain unknown (Totaro et al., 2018). In this work, we set out to find a YAP/TAZ mechano-responsive interactor, that would explain their nuclear accumulation. By considering preliminary data on proteasome localization upon mechanical stimulations, we observed that AMOT proteins are YAP/TAZ cytoplasmic anchors, that get degraded by the mechano-responsive proteasome.