Gene Symbol: PPH3
Description: phosphoprotein phosphatase PP4 catalytic subunit PPH3
Alias: phosphoprotein phosphatase PP4 catalytic subunit PPH3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Van Hoof C, Martens E, Longin S, Jordens J, Stevens I, Janssens V, et al. Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA homologues, Ypa1 and Ypa2. Biochem J. 2005;386:93-102 pubmed
    ..Ypa1 interacts specifically with Pph3, Sit4 and Ppg1, whereas Ypa2 binds to Pph21 and Pph22...
  2. Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J, et al. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2006;439:497-501 pubmed
    ..Here we describe a three-protein complex (HTP-C, for histone H2A phosphatase complex) containing the phosphatase Pph3 that regulates the phosphorylation status of gammaH2AX in vivo and efficiently dephosphorylates gammaH2AX in vitro...
  3. O Neill B, Szyjka S, Lis E, Bailey A, Yates J, Aparicio O, et al. Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc Natl Acad Sci U S A. 2007;104:9290-5 pubmed
    ..Here, we present genetic and biochemical evidence that the type 2A-like protein phosphatase Pph3 forms a complex with Psy2 (Pph3-Psy2) that binds and dephosphorylates activated Rad53 during treatment with, and ..
  4. Szyjka S, Aparicio J, Viggiani C, Knott S, Xu W, Tavare S, et al. Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae. Genes Dev. 2008;22:1906-20 pubmed publisher
    ..Recently, cells lacking the Psy2-Pph3 phosphatase were shown to be defective in dephosphorylation of Rad53 as well as replication fork restart after DNA ..
  5. Lin F, Arndt K. The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis. EMBO J. 1995;14:2745-59 pubmed
    ..These results suggest that PP2A is required during G2 for the activation of Clb-Cdc28 kinase complexes for progression into mitosis. ..
  6. Shen Z, Hsu P, Su Y, Yang C, Kao L, Tseng S, et al. PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase. Nat Commun. 2014;5:5312 pubmed publisher
    ..Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase. ..
  7. Ma H, Han B, Guaderrama M, Aslanian A, Yates J, Hunter T, et al. Psy2 targets the PP4 family phosphatase Pph3 to dephosphorylate Mth1 and repress glucose transporter gene expression. Mol Cell Biol. 2014;34:452-63 pubmed publisher
    ..We address this question by elucidating a novel function of the conserved PP4 family phosphatase Pph3-Psy2, the yeast counterpart of the mammalian PP4c-R3 complex, in the glucose-signaling pathway...
  8. Zhang W, Durocher D. De novo telomere formation is suppressed by the Mec1-dependent inhibition of Cdc13 accumulation at DNA breaks. Genes Dev. 2010;24:502-15 pubmed publisher
    ..Conversely, telomere addition at accidental breaks is promoted by Pph3, the yeast protein phosphatase 4 (PP4). Pph3 is itself modulated by Rrd1, an activator of PP2A family phosphatases...
  9. Herruzo E, Ontoso D, González Arranz S, Cavero S, Lechuga A, San Segundo P. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects. Nucleic Acids Res. 2016;44:7722-41 pubmed publisher
    ..Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. ..

More Information


  1. Hustedt N, Seeber A, Sack R, Tsai Pflugfelder M, Bhullar B, Vlaming H, et al. Yeast PP4 interacts with ATR homolog Ddc2-Mec1 and regulates checkpoint signaling. Mol Cell. 2015;57:273-89 pubmed publisher
    ..one for spontaneous survivors and an E-MAP screen for synthetic growth effects, identified loss of PP4 phosphatase, pph3Δ and psy2Δ, as the strongest suppressors of mec1-100 lethality on HU...
  2. Bertram P, Choi J, Carvalho J, Ai W, Zeng C, Chan T, et al. Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. J Biol Chem. 2000;275:35727-33 pubmed
    ..In contrast to the free Gln3p, the Ure2p-bound Gln3p is signifcantly resistant to dephosphorylation. Taken together, these results reveal a tripartite regulatory mechanism by which the phosphorylation of Gln3p is regulated. ..
  3. Wang H, Wang X, Jiang Y. Interaction with Tap42 is required for the essential function of Sit4 and type 2A phosphatases. Mol Biol Cell. 2003;14:4342-51 pubmed
    ..In addition, we showed that Tap42 is able to interact with two other 2A-like phosphatases, Pph3 and Ppg1.
  4. Bazzi M, Mantiero D, Trovesi C, Lucchini G, Longhese M. Dephosphorylation of gamma H2A by Glc7/protein phosphatase 1 promotes recovery from inhibition of DNA replication. Mol Cell Biol. 2010;30:131-45 pubmed publisher
    ..checkpoint inactivation during methylmethane sulfonate exposure, which instead requires the protein phosphatases Pph3, Ptc2, and Ptc3...
  5. Chan L, Amon A. The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4. Genes Dev. 2009;23:1639-49 pubmed publisher
  6. Guénolé A, Srivas R, Vreeken K, Wang Z, Wang S, Krogan N, et al. Dissection of DNA damage responses using multiconditional genetic interaction maps. Mol Cell. 2013;49:346-58 pubmed publisher
    ..Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways. ..
  7. Oler A, Cairns B. PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. EMBO J. 2012;31:1440-52 pubmed publisher
    ..establish the protein phosphatase 4 (PP4) complex as the main Maf1 phosphatase, and define the involved catalytic (Pph3), scaffold (Psy2) and regulatory subunits (Rrd1, Tip41), as well as uninvolved subunits (Psy4, Rrd2)...
  8. Hu G, Ronne H. Overexpression of yeast PAM1 gene permits survival without protein phosphatase 2A and induces a filamentous phenotype. J Biol Chem. 1994;269:3429-35 pubmed
    ..A third related gene, PPH3, also contributes some PP2A activity...
  9. Vázquez Martin C, Rouse J, Cohen P. Characterization of the role of a trimeric protein phosphatase complex in recovery from cisplatin-induced versus noncrosslinking DNA damage. FEBS J. 2008;275:4211-21 pubmed publisher
    ..that the trimeric Pph3p-Psy4p-Psy2p complex may dephosphorylate both gammaH2AX and Rad53p, the differences lying in the more stable interaction of the Pph3 phosphatase with gammaH2AX as opposed to a transient interaction with Rad53p.
  10. Yang J, Roe S, Prickett T, Brautigan D, Barford D. The structure of Tap42/alpha4 reveals a tetratricopeptide repeat-like fold and provides insights into PP2A regulation. Biochemistry. 2007;46:8807-15 pubmed
    ..We propose a scaffolding function for Tap42/alpha4 whereby the interaction of PP2Ac at its N-terminus promotes the dephosphorylation of substrates recruited to the C-terminal region of the molecule. ..
  11. Hastie C, Vázquez Martin C, Philp A, Stark M, Cohen P. The Saccharomyces cerevisiae orthologue of the human protein phosphatase 4 core regulatory subunit R2 confers resistance to the anticancer drug cisplatin. FEBS J. 2006;273:3322-34 pubmed
    ..A genome-wide screen in Saccharomyces cerevisiae previously identified PPH3 and PSY2 among the top 20 genes conferring resistance to these anticancer agents...
  12. Hoffmann R, Jung S, Ehrmann M, Hofer H. The Saccharomyces cerevisiae gene PPH3 encodes a protein phosphatase with properties different from PPX, PP1 and PP2A. Yeast. 1994;10:567-78 pubmed
    ..Except for replacement of IIe-245 by Met the structure of the phosphatase was identical to that encoded by PPH3 (Ronne, H., Carlberg, M., Hu, G. Z. and Nehlin, J. O. (1991). Mol. Cell. Biochem...
  13. Simoneau A, Ricard Ã, Weber S, Hammond Martel I, Wong L, Sellam A, et al. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress. Nucleic Acids Res. 2016;44:2706-26 pubmed publisher
    ..Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. ..
  14. Wang Y, Ng T. Phosphatase 2A negatively regulates mitotic exit in Saccharomyces cerevisiae. Mol Biol Cell. 2006;17:80-9 pubmed
    ..Genes that encode the B-regulatory subunit (Cdc55) and the three catalytic subunits (Pph21, Pph22, and Pph3) of phosphatase 2A (PP2A) were isolated...
  15. Fong C, Arumugam A, Koepp D. The Saccharomyces cerevisiae F-box protein Dia2 is a mediator of S-phase checkpoint recovery from DNA damage. Genetics. 2013;193:483-99 pubmed publisher
    ..We propose a model in which Dia2 mediates Mrc1 degradation to help cells resume the cell cycle during recovery from MMS-induced DNA damage in S-phase. ..
  16. Au T, Rodriguez J, Vincent J, Tsukiyama T. ATP-dependent chromatin remodeling factors tune S phase checkpoint activity. Mol Cell Biol. 2011;31:4454-63 pubmed publisher
    ..Based on these results, we propose that Isw2 and Ino80 are targeted to stalled replication forks via RPA and directly control the amplitude of S phase checkpoint activity and the subsequent deactivation process. ..
  17. Kim J, Hicks W, Li J, Tay S, Haber J. Protein phosphatases pph3, ptc2, and ptc3 play redundant roles in DNA double-strand break repair by homologous recombination. Mol Cell Biol. 2011;31:507-16 pubmed publisher
    ..of the protein phosphatase 2C (PP2C) family, Ptc2 and Ptc3, as well as the protein phosphatase 4 (PP4) enzyme, Pph3. Here, we demonstrate a new function of these three phosphatases in DSB repair...
  18. Falk J, Chan A, Hoffmann E, Hochwagen A. A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev Cell. 2010;19:599-611 pubmed publisher
    ..Here we identify the phosphatase PP4 (Pph3/Psy2) as a mediator of this process in Saccharomyces cerevisiae...
  19. Zhong Y, Nellimoottil T, Peace J, Knott S, Villwock S, Yee J, et al. The level of origin firing inversely affects the rate of replication fork progression. J Cell Biol. 2013;201:373-83 pubmed publisher
  20. Rossio V, Michimoto T, Sasaki T, Ohbayashi I, Kikuchi Y, Yoshida S. Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the spindle assembly checkpoint. J Cell Sci. 2013;126:4396-405 pubmed publisher
    ..Because the Cdc55-binding proteins Zds1 and Zds2 inhibit both nuclear accumulation of Cdc55 and SAC activity, we propose that spatial control of PP2A by Zds1 family proteins is important for tight control of SAC and mitotic progression. ..
  21. Jablonowski C, Cussiol J, Oberly S, Yimit A, Balint A, Kim T, et al. Termination of Replication Stress Signaling via Concerted Action of the Slx4 Scaffold and the PP4 Phosphatase. Genetics. 2015;201:937-49 pubmed publisher
    ..Cells lacking both SLX4 and the PP4-subunit PPH3 display a synergistic increase in Rad53 signaling and are exquisitely sensitive to the DNA alkylating agent methyl ..
  22. Pal G, Paraz M, Kellogg D. Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1. J Cell Biol. 2008;180:931-45 pubmed publisher
    ..Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression. ..
  23. Travesa A, Duch A, Quintana D. Distinct phosphatases mediate the deactivation of the DNA damage checkpoint kinase Rad53. J Biol Chem. 2008;283:17123-30 pubmed publisher
    ..More recently, the PP2A-like protein phosphatase Pph3 has been shown to be required to dephosphorylate Rad53 after DNA methylation damage in S phase...
  24. Douville J, David J, Lemieux K, Gaudreau L, Ramotar D. The Saccharomyces cerevisiae phosphatase activator RRD1 is required to modulate gene expression in response to rapamycin exposure. Genetics. 2006;172:1369-72 pubmed
    We show that mutants lacking either the phosphatase activator Rrd1 or the phosphatase Pph3 are resistant to rapamycin and that double mutants exhibit a synergistic response...