The abstract is read at the publisher; the summary is JClub's.
HERC1 activity is required for K48-linked ubiquitylation of proteasome 19S subunit PSMC6, and loss of this pathway impairs proteasomal activity in HERC1-deficient cells.
- Why it matters: HERC1-associated neurodevelopmental disease variants likely disrupt proteostasis, but the specific HERC1 substrates and how their regulation affects proteasome function were unclear.
- What they did: Using quantitative proteomics with biotinylated ubiquitin, the study mapped HERC1-dependent ubiquitylation in cells expressing HERC1 with or without ligase activity, then mechanistically tested PSMC6 ubiquitylation and degradation.
- The result: HERC1 selectively ubiquitylates unassembled proteasome subunits for proteasomal degradation; in cells lacking HERC1, proteasome activity is disrupted, and the pathogenic c.1448G>A (p.Gly483Glu) variant impairs PSMC6 ubiquitylation via reduced HERC1–PSMC6 interaction.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.