Disease relevance of CUP9

• An earlier study identified Cup9p as a protein required for an aspect of resistance to copper toxicity in S.cerevisiae [1].

High impact information on CUP9

• These findings identify the physiological rationale for the targeting of Cup9 by Ubr1, and indicate that small compounds may regulate other ubiquitin-dependent pathways [2].
• Cup9p acts as a repressor of PTR2, a gene encoding the transmembrane peptide transporter [1].
• In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal [1].
• Using an ethyl methanesulfonate mutant of a yeast strain in which CUP1 and ACE1 were deleted, we isolated a gene, designated CUP9, which permits yeast cells to grow at high concentrations of environmental copper, most notably when lactate is the sole carbon source [3].
• CUP9 mRNA levels were, however, down regulated by copper when yeast cells were grown with glucose but not with lactate or glycerol-ethanol as the sole carbon source [3].

Other interactions of CUP9

• Previous work demonstrated that dipeptides with destabilizing N-terminal residues allosterically activate UBR1, leading to accelerated in vivo degradation of CUP9 and the induction of PTR2 expression [4].
• UBR1 targets CUP9 through its internal degron [5].

References