The Cdc48-Vms1 complex maintains 26S proteasome architecture.

Area of Science:

• Cell biology
• Molecular biology
• Biochemistry

Background:

• The 26S proteasome degrades ubiquitinated proteins, a process essential for cellular health.
• Cdc48 (cell-division cycle 48) and its cofactors escort substrates to the proteasome, but their roles in assembly are not fully understood.

Purpose of the Study:

• To investigate the role of the conserved Cdc48 cofactor, Vms1 (VCP/Cdc48-associated mitochondrial stress-responsive), in proteasome function and assembly.
• To determine the relationship between Vms1, Cdc48, and proteasome architecture.

Main Methods:

• Utilized yeast genetics to study Vms1 function.
• Analyzed proteasome assembly and ubiquitinated protein levels in Vms1 mutant cells.
• Assessed the impact of Vms1 loss on cell viability.

Main Results:

• Yeast lacking Vms1 accumulate proteasome-targeted ubiquitinated proteins.
• Vms1 mutant cells show increased levels of unassembled proteasome particles.
• Vms1 requires Cdc48 interaction for its role in 26S proteasome assembly, and its absence reduces proteasome levels and cell viability.

Conclusions:

• The Cdc48-Vms1 complex plays an unexpected role in preserving proteasome architecture.
• Disrupted proteasome assembly due to Vms1 loss affects protein turnover and cell viability in aging cells.