Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis.

Conditional regulation of the CTLH E3 ligase complex is linked to ribosome biogenesis through a proteome-wide C-degron pathway.

• Why it matters: Understanding the physiological roles of N-degron and C-degron pathways is limited by the scarcity of confirmed substrates, hindering insights into their biological significance.
• What they did: Researchers developed an expression screening approach to identify human proteins with C-degrons, revealing substrates like ZMYND19, AAMP, and AEN, and examining how CTLH-mediated degradation varies with stimuli such as TNFα and mTOR inhibition.
• The result: The study uncovers a C-degron pathway that connects the conditional activity of the CTLH E3 ligase complex to ribosome maturation, highlighting its role in regulating ribosome biogenesis.