Fig. 2: Collided ribosomes can activate three major response pathways.
From: Quality control and signaling pathways at stalled ribosomes
The disome interface is recognized by the E3 ligase ZNF598, which ubiquitylates 40S proteins such as eS10 and uS10. This modification recruits the ASCC to mediate ribosome splitting. The resulting 60S subunit, still attached to the stalled nascent polypeptide, is then processed by the RQC pathway, which targets the stalled polypeptide for proteasomal degradation. Persistent stalling stress activates broader cellular responses, including the ISR and RSR. These signaling cascades help mitigate stalling and influence cell fate decisions. The RQC, ISR and RSR pathways exhibit cross-talk, with activation of one often suppressing the others. The dominant pathway is probably determined by the severity and duration of ribosome stalling. Ub, ubiquitin; P, phosphate.
