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Gene Review

RTG2  -  Rtg2p

Saccharomyces cerevisiae S288c

Synonyms: NRF588, Retrograde regulation protein 2, YGL252C
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High impact information on RTG2

  • Cells containing null alleles of RTG1 and RTG2 are viable and respiratory competent [1].
  • Here we show that retrograde regulation of the yeast CIT2 gene encoding peroxisomal citrate synthase depends on a new class of upstream activation site element (UASr) and two previously unidentified genes, RTG1 and RTG2 [1].
  • RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus [1].
  • A hypophosphorylated form of Mks1p bound to Rtg2p is inactive [2].
  • Point mutations in the Rtg2p ATP binding domain simultaneously block RS and Mks1p-Rtg2p interaction [2].

Biological context of RTG2

  • Homologues of three of these genes have been implicated in azole and/or drug resistance in Saccharomyces cerevisiae: two of these belong to the family of ABC transporters (PDR5 and PDR16), and one is involved in retrograde signaling from mitochondria to nucleus (RTG2) [3].
  • Thus, the USA+ phenotype of rtg2 Delta strains is not the result generation of the [URE3] prion but is a regulatory effect [4].
  • Thus, RTG2 lies at the nexus of cellular metabolism and genome stability, coordinating two pathways that have opposite effects on yeast longevity [5].
  • The lst8-1 mutation, however, which reduces plasma membrane expression of AAP, cannot bypass the Rtg2p requirement, but still suppresses glutamate repression of RTG target gene expression [6].
  • Here we establish that the likely role of Rtg2 is to antagonize the activity of another protein, Mks1, which we demonstrate is itself a negative regulator of RTG target gene activation [7].

Anatomical context of RTG2


Associations of RTG2 with chemical compounds

  • We have examined whether other genes of the glyoxylate cycle exhibit retrograde regulation and the role of RTG1 and RTG2 in their expression [12].
  • In addition, a genetic analysis revealed an interaction between RTG2 and ASP5 (encoding aspartate amino transferase), thus supporting our hypothesis that RTG2 may be involved in the control of several anaplerotic pathways [13].
  • Because rtg1 Delta or rtg3 Delta mutations or the presence of glutamate do not produce the USA+ phenotype, this is a novel function of Rtg2p [4].
  • Cells containing either the original rtg2-2 mutation or a null rtg2 allele are not petite but show a residual growth on minimum glucose medium with ammonium sulfate as the sole nitrogen source [13].
  • Rtg2p acts upstream of the basic helix-loop-helix/leucine zipper transcription factors, Rtg1p and Rtg3p [14].

Other interactions of RTG2

  • Rtg2p, which is cytoplasmic in both rho(+) and rho(o) cells, is required for the dephosphorylation and nuclear localization of Rtg3p [15].
  • Two genes, RTG1 and RTG2, are required for both basal and elevated expression of CIT2 (Liao, X., and Butow, R. A. (1993) Cell 72, 61-71) [12].
  • The Saccharomyces cerevisiae RTG2 gene is a regulator of aconitase expression under catabolite repression conditions [13].
  • FOB1, which is known to be required for ERC formation, and RTG2 were found to be in converging pathways for ERC production [5].
  • Grr1p polyubiquitinates Mks1p not bound to either Rtg2p or to Bmh1/2p, targeting it for degradation [16].

Analytical, diagnostic and therapeutic context of RTG2


  1. RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus. Liao, X., Butow, R.A. Cell (1993) [Pubmed]
  2. Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p. Liu, Z., Sekito, T., Spírek, M., Thornton, J., Butow, R.A. Mol. Cell (2003) [Pubmed]
  3. Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Kaur, R., Castaño, I., Cormack, B.P. Antimicrob. Agents Chemother. (2004) [Pubmed]
  4. A novel Rtg2p activity regulates nitrogen catabolism in yeast. Pierce, M.M., Maddelein, M.L., Roberts, B.T., Wickner, R.B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Rtg2 protein links metabolism and genome stability in yeast longevity. Borghouts, C., Benguria, A., Wawryn, J., Jazwinski, S.M. Genetics (2004) [Pubmed]
  6. RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. Liu, Z., Sekito, T., Epstein, C.B., Butow, R.A. EMBO J. (2001) [Pubmed]
  7. Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae. Dilova, I., Chen, C.Y., Powers, T. Curr. Biol. (2002) [Pubmed]
  8. Enzymatic and metabolic studies on retrograde regulation mutants of yeast. Small, W.C., Brodeur, R.D., Sandor, A., Fedorova, N., Li, G., Butow, R.A., Srere, P.A. Biochemistry (1995) [Pubmed]
  9. Genome-wide responses to mitochondrial dysfunction. Epstein, C.B., Waddle, J.A., Hale, W., Davé, V., Thornton, J., Macatee, T.L., Garner, H.R., Butow, R.A. Mol. Biol. Cell (2001) [Pubmed]
  10. Comparative analysis of estrogenic activity in sewage treatment plant effluents involving three in vitro assays and chemical analysis of steroids. Rutishauser, B.V., Pesonen, M., Escher, B.I., Ackermann, G.E., Aerni, H.R., Suter, M.J., Eggen, R.I. Environ. Toxicol. Chem. (2004) [Pubmed]
  11. Fish cell lines as versatile tools in ecotoxicology: assessment of cytotoxicity, cytochrome P4501A induction potential and estrogenic activity of chemicals and environmental samples. Fent, K. Toxicology in vitro : an international journal published in association with BIBRA. (2001) [Pubmed]
  12. RTG genes in yeast that function in communication between mitochondria and the nucleus are also required for expression of genes encoding peroxisomal proteins. Chelstowska, A., Butow, R.A. J. Biol. Chem. (1995) [Pubmed]
  13. The Saccharomyces cerevisiae RTG2 gene is a regulator of aconitase expression under catabolite repression conditions. Vélot, C., Haviernik, P., Lauquin, G.J. Genetics (1996) [Pubmed]
  14. Signalling between mitochondria and the nucleus regulates the expression of a new D-lactate dehydrogenase activity in yeast. Chelstowska, A., Liu, Z., Jia, Y., Amberg, D., Butow, R.A. Yeast (1999) [Pubmed]
  15. Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p. Sekito, T., Thornton, J., Butow, R.A. Mol. Biol. Cell (2000) [Pubmed]
  16. A novel degron-mediated degradation of the RTG pathway regulator, Mks1p, by SCFGrr1. Liu, Z., Spírek, M., Thornton, J., Butow, R.A. Mol. Biol. Cell (2005) [Pubmed]
  17. Interaction between Rtg2p and Mks1p in the regulation of the RTG pathway of Saccharomyces cerevisiae. Ferreira Júnior, J.R., Spírek, M., Liu, Z., Butow, R.A. Gene (2005) [Pubmed]
  18. The histone acetyltransferase GCN5 modulates the retrograde response and genome stability determining yeast longevity. Kim, S., Ohkuni, K., Couplan, E., Jazwinski, S.M. Biogerontology. (2004) [Pubmed]
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