Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p.
Activation of retrograde signaling (RS) by mitochondrial dysfunction or by inhibition of TOR kinases in yeast results in nuclear accumulation of the transcription factors, Rtg1p and Rtg3p. This process requires Rtg2p, a novel cytoplasmic protein with an N-terminal ATP binding domain. We show that Rtg2p controls RS by reversibly binding a negative regulator, Mks1p. The inhibitory form of Mks1p is phosphorylated and complexed with the 14-3-3 proteins, Bmh1p and Bmh2p, which are also negative regulators of RS. A hypophosphorylated form of Mks1p bound to Rtg2p is inactive. Point mutations in the Rtg2p ATP binding domain simultaneously block RS and Mks1p-Rtg2p interaction. We propose that activation of RS via mitochondrial dysfunction and TOR inhibition intersect at the Rtg2p-Mks1p switch.
Liu
Zhengchang
Z
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Sekito
Takayuki
T
Spírek
Mário
M
Thornton
Janet
J
Butow
Ronald A
RA
D048948:14-3-3 Proteins; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D015723:Gene Library; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D048948:14-3-3 Proteins; C075852:BMH1 protein, S cerevisiae; C097164:BMH2 protein, S cerevisiae; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; C080921:MKS1 protein, S cerevisiae; C079379:RTG2 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D001616:beta-Galactosidase; D020123:Sirolimus