Disease relevance of BSD2

• A mutation in BSD2 not only reverses the aerobic defects of yeast strains lacking superoxide dismutase but also is associated with an increased sensitivity to copper and cadmium toxicity and an elevation in copper ion accumulation [1].

High impact information on BSD2

• We propose that the Tre proteins specifically link Smf1 to the Bsd2-dependent quality control system [2].
• Degradation requires Bsd2, a membrane protein with a PPxY motif that recruits the ubiquitin ligase Rsp5, and which has a role in the quality control of membrane proteins, that expose hydrophilic residues to the lipid bilayer [2].
• Like Tul1, the Bsd2 system recognises polar TMDs [3].
• Here we show that Bsd2 provides an alternative ubiquitination mechanism for Cps1, Phm5 and other proteins [3].
• Smf1p and Smf2p function in cellular accumulation of manganese, and the two proteins are coregulated by manganese ions and the BSD2 gene product [4].

Biological context of BSD2

• The requirement for yeast superoxide dismutase is bypassed through mutations in BSD2, a novel metal homeostasis gene [1].
• The BSD2 gene was cloned by functional complementation and is predicted to encode a novel 37.5-kDa protein with three potential transmembrane domains [1].
• This substitution results in total inactivation of BSD2, since the bsd2-1 mutation is identical to a bsd2 delta gene deletion in phenotype [1].

Anatomical context of BSD2

• By biochemical fractionation and immunofluorescence microscopy, BSD2 exhibited localization to the endoplasmic reticulum, suggesting that BSD2 acts at a distance to inhibit metal uptake from the growth medium [5].
• Smf3p is not regulated by Bsd2p or by manganese ions and is not degraded in the vacuole [4].
• Genetic suppressor analysis revealed that hyperaccumulation of copper and cadmium in bsd2 mutants is mediated through SMF1, previously shown to encode a plasma membrane transporter for manganese [5].

Associations of BSD2 with chemical compounds

• To our surprise, we found that overexpression of BSD2 rendered yeast cells resistant to adriamycin [6].
• Although both SMF1- and SMF2-disrupted cells were very sensitive to EGTA, overexpression of BSD2 had little or no effect on sensitivity to EGTA [6].
• We demonstrate here that bsd2 mutant cells additionally accumulate high levels of cadmium and cobalt [5].

Regulatory relationships of BSD2

• Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. cerevisiae BSD2 gene [7].

Other interactions of BSD2

• Oxygen toxicity in Saccharomyces cerevisiae strains lacking superoxide dismutase can be suppressed through mutations in either the BSD1 or BSD2 gene [1].

References