Model for translation quality control pathway that resolves PF8503-induced stalling.

PELO/HBS1L detection of PF8503-stalled 80S ribosomes activates a translation quality control pathway that includes ASC-1 (ASCC1-3), which recognizes a K63-linked polyubiquitin signal on the ribosome. These steps are also triggered by HHT. After the 60S subunit is released from the stalled 80S ribosome, RQC may clear the stalled peptidyl-tRNA (LTN1/NEMF). In late steps of recycling, PF8503 bound in the exit tunnel may interfere with quality control functions of ZNF622 and EIF6.