TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acid-sensing pathway in Saccharomyces cerevisiae

Abstract

STP1 gene was found to be hypersensitive to rapamycin, and overexpression of STP1 conferred resistance to rapamycin. Interestingly, we found that the rapamycin-induced disappearance of Stp1 from the nucleus resulted from Stp1 degradation, which was dependent on the activity of a protein phosphatase 2A (PP2A)-like phosphatase, Sit4, which is a wellknown downstream effector of TORC1. Taken together, our findings highlight an intimate connection between the aminoacid-sensing pathway and the rapamycin-sensitive TOR signaling pathway.Key words: TORC1, Rapamycin, Stp1, Sit4, Saccharomyces cerevisiae Summary TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acidsensing pathway in Saccharomyces cerevisiae

Differential Regulation of Transcription Factors Stp1 and Stp2 in the Ssy1-Ptr3-Ssy5 Amino Acid Sensing Pathway

“…Proteasome Function Is Required for Degradation of Fulllength and Processed Stp2-It has been shown that proteasome function is required for degradation of full-length and processed Stp1 (19,24). Therefore, we asked whether protea-some function is also required for turnover of Stp2.…”

“…The AGP1-lacZ fusion gene has been used extensively as a reporter in this pathway (2,11,30,31). Previously, both full-length and processed Stp1 have been reported to be unstable, with a half-life (t1 ⁄ 2 ) of Ͻ10 min for full-length Stp1 (18,24). However, little is known about the stability of Stp2.…”

“…Stp1 is subject to other types of regulation apart from Ssy5-dependent endoproteolytic processing. It has been shown that Stp1 is rapidly turned over and is phosphorylated (8,18,19,24). Rapamycin treatment induces Stp1 degradation, which has been suggested to result from Stp1 dephosphorylation (24).…”

“…It has been shown that Stp1 is rapidly turned over and is phosphorylated (8,18,19,24). Rapamycin treatment induces Stp1 degradation, which has been suggested to result from Stp1 dephosphorylation (24). Although most studies have focused on Stp1, there remains limited understanding of Stp1 degradation with regard to the factors involved.…”

Single yeast cells vary in transcription activity not in delay time after a metabolic shift

“…1a, blue line), that is, before the intracellular methionine concentration depletes significantly, could hint at growth control via extracellular signalling of amino acids 35,36 . The intracellular methionine concentrations during the nutrient downshift decreases from 1 to 0.3 nmol per mg dry weight.…”