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Gene Review

PHO85  -  cyclin-dependent serine/threonine-protein...

Saccharomyces cerevisiae S288c

Synonyms: Cyclin-dependent protein kinase PHO85, Negative regulator of the PHO system, P7102.18A, SSG3, Serine/threonine-protein kinase PHO85, ...
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Disease relevance of PHO85

  • Each of the fusion proteins, LacZ-Pho80 and LacZ-Pho85, was produced into Escherichia coli and used as an antigen to raise antibodies in a rabbit [1].

High impact information on PHO85

  • The ability of cells to react appropriately to nutritional cues is of fundamental importance, and in budding yeast, a small number of intracellular protein kinases, PKA, Snf1p/AMP-activated kinase, TOR, Gcn2p, and the cyclin-dependent kinase Pho85p have key roles [2].
  • We show that phosphorylation of Pho4 by a nuclear complex of a cyclin with a cyclin-dependent kinase, Pho80-Pho85, triggers its export from the nucleus [3].
  • Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase PHO85 [4].
  • A complex consisting of the cyclin-dependent kinase (CDK) PHO85 and the cyclin PHO80 phosphorylates and is thought to inactivate the transcription factor PHO4 when yeast cells are grown in medium containing high concentrations of phosphate [5].
  • Here it is reported that PHO80 has homology to yeast cyclins and interacts with PHO85, a p34cdc2/CDC28-related protein kinase [6].

Biological context of PHO85

  • Analysis of Ser-to-Ala mutations at the three potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or Thr-667 in PHO85 control of glycogen synthase [7].
  • In Saccharomyces cerevisiae, PHO85 encodes a cyclin-dependent protein kinase (Cdk) with multiple roles in cell cycle and metabolic controls [8].
  • Other cellular roles for Pho85 cyclin-Cdk complexes are suggested by the multiple phenotypes associated with deletion of PHO85, in addition to Start defects and deregulated acid phosphatase gene expression [9].
  • We described several unique phenotypes associated with the deletion of the PHO85 gene including growth defects on a variety of carbon sources and hyperaccumulation of glycogen in rich medium high in Pi [10].
  • Our studies suggest that Pho85 associates with multiple cyclins and that subsets of cyclins may direct Pho85 to perform distinct roles in cell growth and division [9].

Anatomical context of PHO85


Associations of PHO85 with chemical compounds

  • However, unlike pho85 mutants, pcl8 pcl10 cells had normal morphologies, grew on glycerol, and showed proper regulation of acid phosphatase gene expression [8].
  • The activity of one of these, GPK2, was inhibited by olomoucine, which potently inhibits cyclin-dependent protein kinases, and contained an approximately 36-kDa species that reacted with antibodies to Pho85p [7].
  • Phosphorylation by Pho85 cyclin-dependent kinase acts as a signal for the down-regulation of the yeast sphingoid long-chain base kinase Lcb4 during the stationary phase [15].
  • In this review we present information on the regulation of the activity of the enzymes implicated in the pathways of synthesis and degradation of glycogen and trehalose as well as on the transcriptional control of the genes encoding them. cAMP and the protein kinases Snf1 and Pho85 appear as major actors in this regulation [16].
  • An in vitro assay showed that a glutathione S-transferase-Pho81p fusion protein inhibits the Pho85p protein kinase [17].

Physical interactions of PHO85

  • Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast [18].
  • Although Pho85 is not essential for viability, Pcl1,2-Pho85 kinase complexes become essential for Start in the absence of Cln1,2-Cdc28 kinases [9].
  • PCL2 interacted with the cdk PHO85 in vivo and in vitro and formed a kinase complex that had G1-periodic activity [19].
  • Additionally, we show that Pcl7 interacts with the phosphate-regulated cyclin-cdk inhibitor Pho81, and that the regulation of the Pcl7-Pho85 complex in response to changes in phosphate levels is dependent on Pho81 [20].
  • Gcn4 degradation depends on the ubiquitination complex SCF(CDC4) and requires phosphorylation by the cyclin-dependent kinase Pho85 [21].

Enzymatic interactions of PHO85

  • The PHO80 protein was found to be phosphorylated in the presence of PHO85 protein [1].
  • Previous work has shown that Rvs167p can be phosphorylated in vitro by the cyclin-dependent kinase Pho85p complexed with its cyclin Pcl2p [22].
  • Pho85 and other G1 Cdks appear to phosphorylate Sic1 at different sites in vivo [23].
  • Many known substrates of the G1 forms of Pho85 are also phosphorylated by the homologous Cdk Cln-Cdc28, suggesting parallel or overlapping roles [24].

Regulatory relationships of PHO85

  • Mutation of the type-1 protein phosphatase encoded by GLC7 only partially suppresses the glycogen phenotype of the pho85 mutant [10].
  • Mutation of PHO85 suppressed the glycogen storage deficiency of snf1 or glc7-1 mutants in which glycogen synthase is locked in an inactive state [8].
  • Two contiguous regions upstream of the GSY2 coding region are necessary for negative control by the cyclin-dependent protein kinase Pho85, one of which is a 14-bp G/C-rich sequence [25].
  • The CDK inhibitor PHO81 inhibits the kinase activity of the PHO80-PHO85 complex when Saccharomyces cerevisiae cells are grown in medium depleted of phosphate [5].
  • We propose that Rvs167p is activated by phosphorylation in its GPA region by the Pcl-Pho85p kinase [26].

Other interactions of PHO85

  • The vacuole inheritance defect in vac5-1 cells is dependent on the presence of the Pho85 kinase and its targets Pho4p and Pho2p [11].
  • Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae [7].
  • In addition, two other G1 cyclins, Pcl1 and Pcl2, associate with a second Cdk, Pho85, to contribute to Start [9].
  • Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants [27].
  • We show that deletion of PHO85, which encodes a cyclin-dependent protein kinase, causes reduced transcription of HO and that this reduction is dependent on ASH1 [28].

Analytical, diagnostic and therapeutic context of PHO85


  1. Negative regulators of the PHO system of Saccharomyces cerevisiae: characterization of PHO80 and PHO85. Uesono, Y., Tokai, M., Tanaka, K., Tohe, A. Mol. Gen. Genet. (1992) [Pubmed]
  2. Nutrient-regulated protein kinases in budding yeast. Wilson, W.A., Roach, P.J. Cell (2002) [Pubmed]
  3. The receptor Msn5 exports the phosphorylated transcription factor Pho4 out of the nucleus. Kaffman, A., Rank, N.M., O'Neill, E.M., Huang, L.S., O'Shea, E.K. Nature (1998) [Pubmed]
  4. Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase PHO85. Espinoza, F.H., Ogas, J., Herskowitz, I., Morgan, D.O. Science (1994) [Pubmed]
  5. Phosphate-regulated inactivation of the kinase PHO80-PHO85 by the CDK inhibitor PHO81. Schneider, K.R., Smith, R.L., O'Shea, E.K. Science (1994) [Pubmed]
  6. Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85. Kaffman, A., Herskowitz, I., Tjian, R., O'Shea, E.K. Science (1994) [Pubmed]
  7. Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae. Huang, D., Farkas, I., Roach, P.J. Mol. Cell. Biol. (1996) [Pubmed]
  8. Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10. Huang, D., Moffat, J., Wilson, W.A., Moore, L., Cheng, C., Roach, P.J., Andrews, B. Mol. Cell. Biol. (1998) [Pubmed]
  9. A family of cyclin-like proteins that interact with the Pho85 cyclin-dependent kinase. Measday, V., Moore, L., Retnakaran, R., Lee, J., Donoviel, M., Neiman, A.M., Andrews, B. Mol. Cell. Biol. (1997) [Pubmed]
  10. Deletion of the gene encoding the cyclin-dependent protein kinase Pho85 alters glycogen metabolism in Saccharomyces cerevisiae. Timblin, B.K., Tatchell, K., Bergman, L.W. Genetics (1996) [Pubmed]
  11. A truncated form of the Pho80 cyclin redirects the Pho85 kinase to disrupt vacuole inheritance in S. cerevisiae. Nicolson, T.A., Weisman, L.S., Payne, G.S., Wickner, W.T. J. Cell Biol. (1995) [Pubmed]
  12. Signaling phosphate starvation. Lenburg, M.E., O'Shea, E.K. Trends Biochem. Sci. (1996) [Pubmed]
  13. Mammalian Cdk5 is a functional homologue of the budding yeast Pho85 cyclin-dependent protein kinase. Huang, D., Patrick, G., Moffat, J., Tsai, L.H., Andrews, B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  14. Microtubule binding and clustering of human Tau-4R and Tau-P301L proteins isolated from yeast deficient in orthologues of glycogen synthase kinase-3beta or cdk5. Vandebroek, T., Terwel, D., Vanhelmont, T., Gysemans, M., Van Haesendonck, C., Engelborghs, Y., Winderickx, J., Van Leuven, F. J. Biol. Chem. (2006) [Pubmed]
  15. Phosphorylation by Pho85 cyclin-dependent kinase acts as a signal for the down-regulation of the yeast sphingoid long-chain base kinase Lcb4 during the stationary phase. Iwaki, S., Kihara, A., Sano, T., Igarashi, Y. J. Biol. Chem. (2005) [Pubmed]
  16. Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. François, J., Parrou, J.L. FEMS Microbiol. Rev. (2001) [Pubmed]
  17. Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the transduction pathway of Pi signals in Saccharomyces cerevisiae. Ogawa, N., Noguchi, K., Sawai, H., Yamashita, Y., Yompakdee, C., Oshima, Y. Mol. Cell. Biol. (1995) [Pubmed]
  18. Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast. Measday, V., McBride, H., Moffat, J., Stillman, D., Andrews, B. Mol. Microbiol. (2000) [Pubmed]
  19. The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast. Measday, V., Moore, L., Ogas, J., Tyers, M., Andrews, B. Science (1994) [Pubmed]
  20. Regulation of the Pcl7-Pho85 cyclin-cdk complex by Pho81. Lee, M., O'Regan, S., Moreau, J.L., Johnson, A.L., Johnston, L.H., Goding, C.R. Mol. Microbiol. (2000) [Pubmed]
  21. Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5. Shemer, R., Meimoun, A., Holtzman, T., Kornitzer, D. Mol. Cell. Biol. (2002) [Pubmed]
  22. Regulation of the yeast amphiphysin homologue Rvs167p by phosphorylation. Friesen, H., Murphy, K., Breitkreutz, A., Tyers, M., Andrews, B. Mol. Biol. Cell (2003) [Pubmed]
  23. Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation. Nishizawa, M., Kawasumi, M., Fujino, M., Toh-e, A. Mol. Biol. Cell (1998) [Pubmed]
  24. Pho85, a multifunctional cyclin-dependent protein kinase in budding yeast. Huang, D., Friesen, H., Andrews, B. Mol. Microbiol. (2007) [Pubmed]
  25. Combinatorial control by the protein kinases PKA, PHO85 and SNF1 of transcriptional induction of the Saccharomyces cerevisiae GSY2 gene at the diauxic shift. Enjalbert, B., Parrou, J.L., Teste, M.A., François, J. Mol. Genet. Genomics (2004) [Pubmed]
  26. In vivo analysis of the domains of yeast Rvs167p suggests Rvs167p function is mediated through multiple protein interactions. Colwill, K., Field, D., Moore, L., Friesen, J., Andrews, B. Genetics (1999) [Pubmed]
  27. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Wang, Z., Wilson, W.A., Fujino, M.A., Roach, P.J. Mol. Cell. Biol. (2001) [Pubmed]
  28. The protein kinase Pho85 is required for asymmetric accumulation of the Ash1 protein in Saccharomyces cerevisiae. McBride, H.J., Sil, A., Measday, V., Yu, Y., Moffat, J., Maxon, M.E., Herskowitz, I., Andrews, B., Stillman, D.J. Mol. Microbiol. (2001) [Pubmed]
  29. A role for the Pcl9-Pho85 cyclin-cdk complex at the M/G1 boundary in Saccharomyces cerevisiae. Tennyson, C.N., Lee, J., Andrews, B.J. Mol. Microbiol. (1998) [Pubmed]
  30. Substrate targeting of the yeast cyclin-dependent kinase Pho85p by the cyclin Pcl10p. Wilson, W.A., Mahrenholz, A.M., Roach, P.J. Mol. Cell. Biol. (1999) [Pubmed]
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