University of Carthage, High Institute of Environmental Sciences and Technologies, Borj-Cedria Science and Technology Park, PB-1003, Hammam-Lif 2050, Tunisia.
Biochem Cell Biol. 2013 Jun;91(3):123-30. doi: 10.1139/bcb-2012-0084. Epub 2012 Dec 10.
In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin mimics starvation by inhibiting the kinase Tor1. We recently documented that this treatment triggers a rapid degradation of Sgs1, a helicase involved in several biological processes such as the prevention of genomic instability. Herein, we show that yeast strains deleted for genes ATG2, ATG9, and PEP4, encoding components of the autophagy pathway, prevent rapamycin-induced degradation of Sgs1. We propose that defects in the autophagy pathway prevent degradation of key proteins in the rapamycin response pathway and as a consequence cause resistance to the drug.
在酵母酿酒酵母中,免疫抑制剂雷帕霉素通过抑制激酶 Tor1 模拟饥饿。我们最近的研究表明,这种治疗方法会迅速导致 Sgs1 的降解,Sgs1 是一种参与多种生物学过程的解旋酶,如防止基因组不稳定性。在此,我们表明,缺失编码自噬途径成分的 ATG2、ATG9 和 PEP4 基因的酵母菌株可防止雷帕霉素诱导的 Sgs1 降解。我们提出,自噬途径的缺陷阻止了雷帕霉素反应途径中关键蛋白的降解,因此导致对该药物的抗性。