Conditional CTLH E3 ligase C-degron pathway tied to ribosome biogenesis
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A proteome-wide study by Grant et al., published in Molecular Cell on October 20, 2026, mapped C-degron activity across the human proteome using ORFeome libraries with different C-terminal architectures for comparative stability profiling. The work identified a conditionally regulated C-degron pathway controlled by the CTLH/Muskelin E3 ubiquitin ligase complex. One substrate, AAMP, is the human ortholog of yeast Sqt1 and functions as a chaperone for the ribosomal protein uL16. This connects nutrient status to the control of ribosome biogenesis, positioning the CTLH complex as a condition-sensitive regulator of a core cellular process. Which nutrients and signals gate the pathway, and the full range of its substrates, are open questions.
Written by a model from the reports · updated 2 hours ago
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- CellPickProteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis
Grant et al. used ORFeome libraries with different C-terminal architectures for comparative stability profiling and identified a conditionally regulated C-degron pathway controlled by the CTLH/Muskelin E3 ubiquitin ligase complex. Its substrate AAMP is the human ortholog of yeast Sqt1 and acts as a uL16 chaperone, linking nutrient status to the regulation of ribosome biogenesis.
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