The cancer-associated human ubiquitin ligase HUWE1 can adopt an auto-inhibited dimeric state, whose occupancy is regulated by competing intra- and intermolecular interactions of the dimerization region and by the tumor suppressor p14ARF.
Engineered E3 ubiquitin ligases are utilized to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve robust post-translational functional knockdown of ion channels.
E3 ubiquitin ligase Bre1-induced H2B monoubiquitination is epigenetically important for recruiting replication factor Mcm10 and cohesion establishment factors Ctf4, Ctf18 and Eco1 to early replication origins to establish sister chromatid cohesion.
CRISPR/Cas9 genome-wide screens using sterol-sensitive endogenous HMG-CoA reductase (HMGCR) reporter identify the sterol-responsive RNF145 and gp78 as independently responsible for sterol-accelerated degradation of HMGCR, the rate-limiting enzyme of cholesterol biosynthesis.
Human cullin-RING ligases are buffered to a much greater extent than had been previously appreciated, and the roles of ubiquitin chain extension enzymes are far more nuanced at physiological concentrations.