U7BR contact residues are essential in vivo for Ubc7p’s
stability, binding to Cue1p, and ERAD. (A) Degradation of Ubc7pHA and
GFP-Cue1p110-203 were assessed by cycloheximide (CHX) chase at the indicated
time points using a ubc7Δ cue1Δ strain containing a
chromosomal CPY* allele transformed with a low copy plasmid encoding Ubc7pHA and
low copy plasmids encoding vector (pRS314) or the indicated GFP-Cue1p110-203
wild-type- or mutant-expressing plasmid. Protein stability was analyzed by SDS-PAGE and
immunoblotting with anti-HA and anti-GFP antibodies, respectively. PGK was used as a
loading control. (B) The binding of transmembrane anchored TMUbc7pHA to the
indicated GFP-Cue1p110-203 wild-type or U7BR mutant was assessed by
co-immunoprecipitation of TMUbc7pHA from equivalent amounts of
detergent-solubilized protein lysates using anti-HA affinity matrix. Bound proteins were
eluted, analyzed by SDS-PAGE, and TMUbc7pHA and GFP-Cue1p110-203
wild-type and indicated mutants were visualized by immunoblotting with anti-HA and
anti-Cue1p antibodies, respectively. 10% of each input lysate was also analyzed.
(C) The degradation of CPY* was analyzed at the indicated time points by
35S pulse-chase analysis using the indicated strain carrying vector (pRS314)
or wild-type GFP-Cue1p110-203. (D) The average of three independent pulse-chase
experiments of the GFP-Cue1p110-203 wild-type and mutant strains from (B).
Error bars represent the standard error. (E) The half-life (t1/2, in min) of
CPY* in each of the strains was calculated from the graphs in (D).