Identification of a quality-control factor that monitors failures during proteasome assembly

Safeguarding protein complex assembly The assembly of multiprotein complexes inside the cell requires each subunit to be produced at a defined level relative to its partners. Imbalances in subunit synthesis are inevitable, necessitating the elimination of unassembled intermediates. Zavodszky et al . found that a ubiquitin ligase called HERC1 is responsible for marking certain assembly intermediates of the proteasome for degradation. HERC1 finds these intermediates by recognizing a proteasome assembly factor that normally dissociates when assembly is complete. A point mutation in HERC1 that impairs its ability to recognize proteasome assembly intermediates causes neurodegeneration in mice, highlighting the importance of this quality control pathway. —SMH