Modification of Cul1 regulates its association with proteasomal subunits

Background: Ubiquitylation targets proteins for degradation by the 26S proteasome. Some yeast
and plant ubiquitin ligases, including the highly conserved SCF (Skp1/Cul1/F-box protein) complex,
have been shown to associate with proteasomes. We sought to characterize interactions between
SCF complexes and proteasomes in mammalian cells.
Results: We found that the binding of SCF complexes to proteasomes is conserved in higher
eukaryotes. The Cul1 subunit associated with both sub-complexes of the proteasome, and high
molecular weight forms of Cul1 bound to the 19S proteasome. Cul1 is ubiquitylated in vivo.
Ubiquitylation of Cul1 promotes its binding to the S5a subunit of the 19S sub-complex without
affecting Cul1 stability.
Conclusion: The association of ubiquitylating enzymes with proteasomes may be an additional
means to target ubiquitylated substrates for degradation.