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Gene Review

PHO80  -  Pho80p

Saccharomyces cerevisiae S288c

Synonyms: AGS3, Aminoglycoside antibiotic sensitivity protein 3, O2505, PHO85 cyclin PHO80, Phosphate system cyclin PHO80, ...
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Disease relevance of PHO80

  • 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 PHO80

  • To investigate the mechanism, we replaced the PHO80 gene, a negative regulator of PHO5, by a temperature-sensitive allele [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].
  • Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85 [4].
  • Under conditions of constitutive submaximal activation (i.e., in the absence of the negative regulator Pho80), deletion of Gcn5 determines a novel randomized nucleosomal organization across the promoter and leads to a dramatic reduction in activity [5].
  • Thus, Rim15 plays a key role in G0 entry through its ability to integrate signaling from the PKA, TORC1, and Pho80-Pho85 pathways [6].

Biological context of PHO80

  • Moreover, in the absence of PHO80, the corepressor, presumed to be a metabolite of Pi, did not inhibit their function in the transcriptional activation of APase [7].
  • Most interestingly, under low phosphate conditions, the An-PHO80 cyclin also promotes sexual development while having a negative effect on asexual development [8].
  • A centromere sequence was found downstream of the PHO80 coding region [9].
  • Coordinate increases of PHO80 and PHO2 give rise to the same phenotype as an increased dosage of PHO80 alone [10].
  • The 1.8 kb DNA fragment carrying the PHO80 gene was sequenced and one open reading frame large enough to encode 293 amino acids was found in the sequence [9].

Anatomical context of PHO80

  • Though vac5-1 is recessive, pho80 delta or pho85 delta strains do not show a defect in vacuole inheritance, suggesting that vac5-1 is not a complete loss-of-function allele [11].
  • Immunoblotting studies reveal that cytosolic AGS3 can remove G(i)alpha subunits from the membrane and sequester G(i)alpha subunits in the cytosol [12].

Associations of PHO80 with chemical compounds

  • Yeast mutants permeable to dTMP (tup) were selected and two new complementation groups (tup5 and tup7) were identified [13].
  • Spontaneously arising extragenic suppressors of cep1 methionine auxotrophy were also isolated; approximately one-third of them were alleles of pho80 [14].
  • The tup7 mutation increased permeability to dTMP (and some other 5'-mononucleotides), but did not affect uptake of nucleosides and purine and pyrimidine bases [15].
  • The auxotrophic requirement of dcd1 dmp1 tup7 strains also can be satisfied by exogenous dTMP but not deoxyuridine [16].
  • The AGS3 GPR domain markedly inhibited the rates of spontaneous guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding to G(i)alpha and rhodopsin-stimulated GTPgammaS binding to G(t)alpha [17].

Physical interactions of PHO80

  • Pho81 forms a stable complex with Pho80-Pho85 under both high- and low-phosphate conditions, but it only inhibits the kinase when cells are starved for phosphate [18].
  • Here, we show that the poorly characterized Pho80-like protein Pcl7 forms a functional kinase complex with the Pho85 cdk, and that the activity of this complex is inhibited in response to phosphate starvation [19].
  • It further showed two sites on the Pho80 cyclin for high-affinity binding of the transcription factor substrate (Pho4) and the CDK inhibitor (Pho81) that are markedly distant to each other and the active site [20].

Enzymatic interactions of PHO80


Regulatory relationships of PHO80

  • More detailed investigation of APase synthesis is a conditional PHO80(Ts) mutant indicated that neither PHO4 nor any other protein factor necessary for APase mRNA synthesis is transcriptionally regulated by PHO80 [7].
  • Furthermore, high levels of PHO80 were shown to suppress the effect of a PHO85 deletion at a level close to full repression [22].
  • Also, 10 independent single-amino-acid changes within PHO80 which resulted in the failure to repress PHO5 transcription were isolated [22].
  • Our results suggest that Pho81 inhibits Pho80-Pho85 with a novel motif [18].

Other interactions of PHO80

  • Thus, both the Pho80p-Pho85p kinase complex (by Pho4p phosphorylation) and a novel component of the N glycosylation pathway contribute to basal levels of aminoglycoside resistance in Saccharomyces cerevisiae [23].
  • High-level expression of Pho80p results in aberrant PHO5 promoter regulation, characterized by failure to derepress in low-phosphate medium [24].
  • This suggests that PHO81 may function by interacting with PHO80 or that these molecules compete for the same target [25].
  • In addition, the chromosome contains two other phenotypic marker genes, HIS3 which is located distal from URA3, and PHO80 which is closely linked to the centromere [26].
  • Importantly, we also show that Pho80-Pho85 and TORC1 converge on a single amino acid in Rim15 [6].

Analytical, diagnostic and therapeutic context of PHO80


  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. Nucleosome disruption at the yeast PHO5 promoter upon PHO5 induction occurs in the absence of DNA replication. Schmid, A., Fascher, K.D., Hörz, W. Cell (1992) [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. 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]
  5. Absence of Gcn5 HAT activity defines a novel state in the opening of chromatin at the PHO5 promoter in yeast. Gregory, P.D., Schmid, A., Zavari, M., Lui, L., Berger, S.L., Hörz, W. Mol. Cell (1998) [Pubmed]
  6. Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex. Wanke, V., Pedruzzi, I., Cameroni, E., Dubouloz, F., De Virgilio, C. EMBO J. (2005) [Pubmed]
  7. Regulation of repressible acid phosphatase gene transcription in Saccharomyces cerevisiae. Lemire, J.M., Willcocks, T., Halvorson, H.O., Bostian, K.A. Mol. Cell. Biol. (1985) [Pubmed]
  8. The Pho80-like cyclin of Aspergillus nidulans regulates development independently of its role in phosphate acquisition. Wu, D., Dou, X., Hashmi, S.B., Osmani, S.A. J. Biol. Chem. (2004) [Pubmed]
  9. Cloning and sequencing of the PHO80 gene and CEN15 of Saccharomyces cerevisiae. Toh-e, A., Shimauchi, T. Yeast (1986) [Pubmed]
  10. Function of the PHO regulatory genes for repressible acid phosphatase synthesis in Saccharomyces cerevisiae. Yoshida, K., Ogawa, N., Oshima, Y. Mol. Gen. Genet. (1989) [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. Influence of cytosolic AGS3 on receptor--G protein coupling. Ma, H., Peterson, Y.K., Bernard, M.L., Lanier, S.M., Graber, S.G. Biochemistry (2003) [Pubmed]
  13. Mutations in the pho80 gene confer permeability to 5'-mononucleotides in Saccharomyces cerevisiae. Bisson, L.F., Thorner, J. Genetics (1982) [Pubmed]
  14. Possible cross-regulation of phosphate and sulfate metabolism in Saccharomyces cerevisiae. O'Connell, K.F., Baker, R.E. Genetics (1992) [Pubmed]
  15. Exogenous dTMP utilization by a novel tup mutant of Saccharomyces cerevisiae. Bisson, L.F., Thorner, J. J. Bacteriol. (1982) [Pubmed]
  16. Isolation of a Saccharomyces cerevisiae mutant strain deficient in deoxycytidylate deaminase activity and partial characterization of the enzyme. McIntosh, E.M., Haynes, R.H. J. Bacteriol. (1984) [Pubmed]
  17. AGS3 inhibits GDP dissociation from galpha subunits of the Gi family and rhodopsin-dependent activation of transducin. Natochin, M., Lester, B., Peterson, Y.K., Bernard, M.L., Lanier, S.M., Artemyev, N.O. J. Biol. Chem. (2000) [Pubmed]
  18. Functional analysis of the cyclin-dependent kinase inhibitor Pho81 identifies a novel inhibitory domain. Huang, S., Jeffery, D.A., Anthony, M.D., O'Shea, E.K. Mol. Cell. Biol. (2001) [Pubmed]
  19. 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]
  20. Structure of the Pho85-Pho80 CDK-cyclin complex of the phosphate-responsive signal transduction pathway. Huang, K., Ferrin-O'Connell, I., Zhang, W., Leonard, G.A., O'Shea, E.K., Quiocho, F.A. Mol. Cell (2007) [Pubmed]
  21. Regulation by phosphorylation of Pho81p, a cyclin-dependent kinase inhibitor in Saccharomyces cerevisiae. Knight, J.P., Daly, T.M., Bergman, L.W. Curr. Genet. (2004) [Pubmed]
  22. Molecular and expression analysis of the negative regulators involved in the transcriptional regulation of acid phosphatase production in Saccharomyces cerevisiae. Madden, S.L., Johnson, D.L., Bergman, L.W. Mol. Cell. Biol. (1990) [Pubmed]
  23. A small protein (Ags1p) and the Pho80p-Pho85p kinase complex contribute to aminoglycoside antibiotic resistance of the yeast Saccharomyces cerevisiae. Wickert, S., Finck, M., Herz, B., Ernst, J.F. J. Bacteriol. (1998) [Pubmed]
  24. Function of hybrid human-yeast cyclin-dependent kinases in Saccharomyces cerevisiae. Bitter, G.A. Mol. Gen. Genet. (1998) [Pubmed]
  25. Molecular analysis of the PHO81 gene of Saccharomyces cerevisiae. Creasy, C.L., Madden, S.L., Bergman, L.W. Nucleic Acids Res. (1993) [Pubmed]
  26. Reciprocal mitotic recombination is the predominant mechanism for the loss of a heterozygous gene in Saccharomyces cerevisiae. Acuña, G., Würgler, F.E., Sengstag, C. Environ. Mol. Mutagen. (1994) [Pubmed]
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