Mks1p is required for negative regulation of retrograde gene expression in Saccharomyces cerevisiae but does not affect nitrogen catabolite repression-sensitive gene expression.
The Tor1/2p signal transduction pathway regulates nitrogen catabolite repression (NCR)-sensitive (GAP1, GAT1, DAL5) and retrograde (CIT2, DLD3, IDH1/2) gene expression by controlling intracellular localization of the transcription activators, Gln3p and Gat1p, and Rtg1p and Rtg3p, respectively. The accepted pathway for this regulation is NH(3) or excess nitrogen dash, vertical Mks1p dash, vertical Ure2p dash, vertical Gln3p --> DAL5, and rapamycin or limiting nitrogen dash, vertical Torp --> Tap42 dash, vertical Mks1p --> Rtg1/3p --> CIT2, respectively. In current models, Mks1p positively regulates both Gln3p (and DAL5 expression) and Rtg1/3p (and CIT2 expression). Here, in contrast, we show the following. (i) Mks1p is a strong negative regulator of CIT2 expression and does not effect NCR-sensitive expression of DAL5 or GAP1. (ii) Retrograde carbon and NCR-sensitive nitrogen metabolism are not linked by the quality of the nitrogen source, i.e. its ability to elicit NCR, but by the product of its catabolism, i.e. glutamate or ammonia. (iii) In some instances, we can dissociate rapamycin-induced CIT2 expression from Mks1p function, i.e. rapamycin does not suppress Mks1p-mediated down-regulation of CIT2 expression. These findings suggest that currently accepted models of Tor1/2p signal transduction pathway regulation require revision.
Tate
Jennifer J
JJ
Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 38120, USA.
Cox
Kathleen H
KH
Rai
Rajendra
R
Cooper
Terrance G
TG
D001483:Base Sequence; D017931:DNA Primers; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology*; D005800:Genes, Fungal; D009584:Nitrogen / Q000378:metabolism*; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors
D017931:DNA Primers; D005656:Fungal Proteins; C080921:MKS1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D009584:Nitrogen; D020123:Sirolimus