Disease relevance of RTG3

• These genes include approximately 60 elements that could be linked to the reported phenotypes of the bmhDelta mutant (e.g., accumulation of glycogen and hypersensitivity to environmental stress) and/or could be the potential downstream targets of interacting partners of Bmh1/2p such as Msn2p and Rtg3p [1].

High impact information on RTG3

• Remarkably, nuclear accumulation of Rtg1/Rtg3, as well as expression of their target genes, is induced by addition of rapamycin, a specific inhibitor of the target of rapamycin (TOR) kinases [2].
• We demonstrate further that Rtg3 is a phosphoprotein and that its phosphorylation state changes after rapamycin treatment [2].
• Expression of these genes in media containing urea or ammonia as a sole nitrogen source requires the heterodimeric bZip transcription factors Rtg1 and Rtg3 and correlates with a redistribution of the Rtg1p/Rtg3 complex from a predominantly cytoplasmic to a predominantly nuclear location [2].
• MSX-induced glutamine starvation caused nuclear localization and activation of the TOR-inhibited transcription factors GLN3, RTG1, and RTG3, all of which mediate glutamine synthesis [3].
• Here, we describe the cloning and characterization of RTG3, a gene encoding a 54-kDa bHLH/Zip protein that is also required for CIT2 expression [4].

Biological context of RTG3

• Recessive mutations in SIN4 and RTG3 can suppress the temperature-sensitive phenotype of this mutant [5].
• The R box is a binding site for Rtg1p-Rtg3p, a heterodimeric, basic helix-loop-helix/leucine zipper transcription factor complex [6].
• Our data show that Rtg1p acts as both a positive and negative regulator of the retrograde response and that Rtg2p acts to transduce mitochondrial signals affecting the phosphorylation state and subcellular localization of Rtg3p [7].
• Two unresolved discrepancies exist with regard to the mechanism of RTG target gene control: (1) deletion of MKS1 results in constitutive expression of RTG target genes in most but not all strain backgrounds; and (2) RTG target gene expression has been correlated with both decreased as well as increased Rtg3p phosphorylation [8].
• We have also identified a serine/threonine-rich domain of Rtg3p within amino acids 176-282 that is inhibitory to transactivation [9].

Anatomical context of RTG3

• Rtg2p is the retrograde signal transducer proximal to the mitochondrion, and it interacts with several proteins in relaying the retrograde signal to the transcription factor Rtg1p-Rtg3p [10].

Associations of RTG3 with chemical compounds

• Our data show that the yeast 14-3-3 proteins negatively regulate Rtg3-dependent transcription, stimulate the transcription of genes involved in ergosterol metabolism and in stress response and are involved in transcription regulation of multiple other genes [11].
• The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine [3].
• Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors [2].
• The heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p regulate the expression of a concise set of metabolic genes (termed RTG target genes) required for de novo biosynthesis of glutamate and glutamine [12].

Physical interactions of RTG3

• TOR acts in part by regulating the subcellular localization of the Rtg1/Rtg3 transcription factor complex [13].
• Here we show that fusion constructs between the Gal4p DNA binding domain and Rtg3p transactivate the expression of a LacZ reporter gene under the control of a GAL1 promoter element [9].

Other interactions of RTG3

• Rtg2p regulates transcription of glutamate-repressible genes by facilitation of the nuclear entry of the Rtg1 and Rtg3 proteins [14].
• Rtg2p, which is cytoplasmic in both rho(+) and rho(o) cells, is required for the dephosphorylation and nuclear localization of Rtg3p [7].
• First, we demonstrate that the mks1 deletion strain used in a previous study by Shamji and coworkers contains a nonsense mutation within codon Ser 231 in RTG3 that likely accounts for the inactivity of the RTG system in this strain [8].

Analytical, diagnostic and therapeutic context of RTG3

• Furthermore, deletion of RTG3, a downstream mediator in this pathway, and caloric restriction had an additive effect, resulting in the largest increase (123%) in longevity described thus far in yeast [15].

References