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Gene Review

MKS1  -  Mks1p

Saccharomyces cerevisiae S288c

Synonyms: LYS80, N2344, N2347, Negative regulator of RAS-cAMP pathway, YNL076W
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High impact information on MKS1

  • A hypophosphorylated form of Mks1p bound to Rtg2p is inactive [1].
  • 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 [1].
  • Point mutations in the Rtg2p ATP binding domain simultaneously block RS and Mks1p-Rtg2p interaction [1].
  • Analyses of transgenic plants and genome-wide transcript profiling indicated that MKS1 is required for full SA-dependent resistance in mpk4 mutants, and that overexpression of MKS1 in wild-type plants is sufficient to activate SA-dependent resistance, but does not interfere with induction of a defense gene by JA [2].
  • Conversely, deletion of MKS1, which increases glutamate and glutamine synthesis, decreases Gap1p sorting to the plasma membrane [3].

Biological context of MKS1

  • 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 [4].
  • Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes [5].
  • 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 [6].
  • The increased production of lysine in lys80 mutants appeared to result from an improvement of the metabolic flux through the pathway and was correlated to an increase of the alpha-ketoglutarate pool and of the level of several enzymes of the tricarboxylic acid cycle [7].

Anatomical context of MKS1


Associations of MKS1 with chemical compounds

  • This latter result provides a molecular explanation for the previous identification of MKS1 as LYS80, a negative regulator of lysine biosynthesis [8] [6].
  • Moreover, overexpression of Ure2p suppresses the ability of Mks1p overexpression to allow ureidosuccinate uptake on ammonia [9].
  • An mks1 ure2 double mutant can take up ureidosuccinate on either ammonia or proline [9].
  • We find that glutamate suppresses [URE3] formation, suggesting that the Mks1p effect on the formation of [URE3] can occur indirectly via regulation of the RTG pathway [8].

Other interactions of MKS1

  • We find that overproduction of Mks1p allows uptake of ureidosuccinate on ammonia and lack of Mks1p prevents uptake of ureidosuccinate or Dal5p expression on proline [9].
  • 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 [4].
  • Overexpression of Mks1p does not affect cellular levels of Ure2p [9].
  • Mks1p is negatively regulated by binding to Rtg2p and positively regulated when bound to Bmh1/2p [10].
  • We show that Rtg2p controls RS by reversibly binding a negative regulator, Mks1p [1].

Analytical, diagnostic and therapeutic context of MKS1


  1. 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]
  2. The MAP kinase substrate MKS1 is a regulator of plant defense responses. Andreasson, E., Jenkins, T., Brodersen, P., Thorgrimsen, S., Petersen, N.H., Zhu, S., Qiu, J.L., Micheelsen, P., Rocher, A., Petersen, M., Newman, M.A., Bjørn Nielsen, H., Hirt, H., Somssich, I., Mattsson, O., Mundy, J. EMBO J. (2005) [Pubmed]
  3. Amino acids regulate the intracellular trafficking of the general amino acid permease of Saccharomycescerevisiae. Chen, E.J., Kaiser, C.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. Accounting for strain-specific differences during RTG target gene regulation in Saccharomyces cerevisiae. Dilova, I., Powers, T. FEMS Yeast Res. (2006) [Pubmed]
  5. Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes. Dilova, I., Aronova, S., Chen, J.C., Powers, T. J. Biol. Chem. (2004) [Pubmed]
  6. 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]
  7. Lys80p of Saccharomyces cerevisiae, previously proposed as a specific repressor of LYS genes, is a pleiotropic regulatory factor identical to Mks1p. Feller, A., Ramos, F., Piérard, A., Dubois, E. Yeast (1997) [Pubmed]
  8. RTG-dependent mitochondria-to-nucleus signaling is regulated by MKS1 and is linked to formation of yeast prion [URE3]. Sekito, T., Liu, Z., Thornton, J., Butow, R.A. Mol. Biol. Cell (2002) [Pubmed]
  9. Mks1p is a regulator of nitrogen catabolism upstream of Ure2p in Saccharomyces cerevisiae. Edskes, H.K., Hanover, J.A., Wickner, R.B. Genetics (1999) [Pubmed]
  10. 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]
  11. 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]
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