Uracil-Induced Down-Regulation of the Yeast Uracil Permease

AUTOR(ES)

Séron, Karin

FONTE

American Society for Microbiology

RESUMO

In Saccharomyces cerevisiae the FUR4-encoded uracil permease catalyzes the first step of the pyrimidine salvage pathway. The availability of uracil has a negative regulatory effect upon its own transport. Uracil causes a decrease in the level of uracil permease, partly by decreasing the FUR4 mRNA level in a promoter-independent fashion, probably by increasing its instability. Uracil entry also triggers more rapid degradation of the existing permease by promoting high efficiency of ubiquitination of the permease that signals its internalization. A direct binding of intracellular uracil to the permease is possibly involved in this feedback regulation, as the behavior of the permease is similar in mutant cells unable to convert intracellular uracil into UMP. We used cells impaired in the ubiquitination step to show that the addition of uracil produces rapid inhibition of uracil transport. This may be the first response prior to the removal of the permease from the plasma membrane. Similar down-regulation of uracil uptake, involving several processes, was observed under adverse conditions mainly corresponding to a decrease in the cellular content of ribosomes. These results suggest that uracil of exogenous or catabolic origin down-regulates the cognate permease to prevent buildup of excess intracellular uracil-derived nucleotides.

Documentos Relacionados

• Nef-Induced Major Histocompatibility Complex Class I Down-Regulation Is Functionally Dissociated from Its Virion Incorporation, Enhancement of Viral Infectivity, and CD4 Down-Regulation
• SoxRS Down-Regulation of rob Transcription
• SCFHOS ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-α receptor
• Down-regulation of beta-adrenergic receptors: agonist-induced reduction in receptor mRNA levels.
• Mechanism for down-regulation of CD28 by Nef