PPH21

Summary

Gene Symbol: PPH21
Description: phosphoprotein phosphatase 2A catalytic subunit PPH21
Alias: phosphoprotein phosphatase 2A catalytic subunit PPH21
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Georis I, Tate J, Feller A, Cooper T, Dubois E. Intranuclear function for protein phosphatase 2A: Pph21 and Pph22 are required for rapamycin-induced GATA factor binding to the DAL5 promoter in yeast. Mol Cell Biol. 2011;31:92-104 pubmed publisher
    Protein phosphatase 2A (PP2A), a central Tor pathway phosphatase consisting of a catalytic subunit (Pph21 or Pph22), a scaffold subunit (Tpd3), and one of two regulatory subunits (Cdc55 or Rts1), has been repeatedly shown to play ..
  2. Sneddon A, Cohen P, Stark M. Saccharomyces cerevisiae protein phosphatase 2A performs an essential cellular function and is encoded by two genes. EMBO J. 1990;9:4339-46 pubmed
    Two genes (PPH21 and PPH22) encoding the yeast homologues of protein serine-threonine phosphatase 2A have been cloned from a Saccharomyces cerevisiae genomic library using a rabbit protein phosphatase 2A cDNA as a hybridization probe...
  3. Jiang Y, Broach J. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J. 1999;18:2782-92 pubmed
    ..of a protein, Tap42, with two different protein phosphatase catalytic subunits; one encoded redundantly by PPH21 and PPH22, and one encoded by SIT4...
  4. 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...
  5. Wicky S, Tjandra H, Schieltz D, Yates J, Kellogg D. The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase. Mol Biol Cell. 2011;22:20-32 pubmed publisher
    ..Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis. ..
  6. Yang H, Jiang W, Gentry M, Hallberg R. Loss of a protein phosphatase 2A regulatory subunit (Cdc55p) elicits improper regulation of Swe1p degradation. Mol Cell Biol. 2000;20:8143-56 pubmed
    ..We also present evidence indicating that, in cdc55-null cells, misregulated PP2A phosphatase activity is the cause of both the ectopic stabilization of Swe1p and the production of the morphologically abnormal phenotype. ..
  7. 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. ..
  8. Wang Y, Burke D. Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple functions in mitosis and is required for the kinetochore/spindle checkpoint in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17:620-6 pubmed
    ..Finally, cdc55::LEU2 suppresses the temperature sensitivity of cdc20-1, suggesting additional roles for CDC55 in mitosis. ..
  9. Shu Y, Yang H, Hallberg E, Hallberg R. Molecular genetic analysis of Rts1p, a B' regulatory subunit of Saccharomyces cerevisiae protein phosphatase 2A. Mol Cell Biol. 1997;17:3242-53 pubmed
    ..Genetic analyses show that the role played by Rts1p in PP2A regulation is distinctly different from that played by the other known variable B regulatory subunit, Cdc55p, a protein recently implicated in checkpoint control regulation. ..

More Information

Publications51

  1. Yan G, Shen X, Jiang Y. Rapamycin activates Tap42-associated phosphatases by abrogating their association with Tor complex 1. EMBO J. 2006;25:3546-55 pubmed
    ..In addition, our data support a model in which rapamycin acts not by inhibiting the kinase activity of Tor but by disrupting its interaction with downstream targets. ..
  2. Harvey S, Enciso G, Dephoure N, Gygi S, Gunawardena J, Kellogg D. A phosphatase threshold sets the level of Cdk1 activity in early mitosis in budding yeast. Mol Biol Cell. 2011;22:3595-608 pubmed publisher
    ..These results define a new role for PP2A(Cdc55) and reveal a systems-level mechanism by which dynamically opposed kinase and phosphatase activities can modulate signal strength. ..
  3. Hombauer H, Weismann D, Mudrak I, Stanzel C, Fellner T, Lackner D, et al. Generation of active protein phosphatase 2A is coupled to holoenzyme assembly. PLoS Biol. 2007;5:e155 pubmed
    ..We propose a novel model of PP2A biogenesis in which a tightly controlled activation cascade protects cells from untargeted activity of the free catalytic PP2A subunit. ..
  4. Wang H, Jiang Y. The Tap42-protein phosphatase type 2A catalytic subunit complex is required for cell cycle-dependent distribution of actin in yeast. Mol Cell Biol. 2003;23:3116-25 pubmed
    ..In addition, we provide evidence that PP2A activity plays a negative role in controlling the actin cytoskeleton and, possibly, in regulation of the G(2)/M transition of the cell cycle. ..
  5. Van Hoof C, Janssens V, De Baere I, Stark M, de Winde J, Winderickx J, et al. The Saccharomyces cerevisiae phosphotyrosyl phosphatase activator proteins are required for a subset of the functions disrupted by protein phosphatase 2A mutations. Exp Cell Res. 2001;264:372-87 pubmed
    ..Therefore, Ypa does not seem to play a role in the regulation of PP2A at this stage of the cell cycle. These results imply that Ypa regulates a specific subset of PP2A functions, possibly by controlling the subunit composition of PP2A. ..
  6. Wei H, Ashby D, Moreno C, Ogris E, Yeong F, Corbett A, et al. Carboxymethylation of the PP2A catalytic subunit in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p. J Biol Chem. 2001;276:1570-7 pubmed
    ..Taken together, our results indicate that methylation and phosphorylation may be mechanisms by which the cell dynamically regulates PP2A complex formation and function. ..
  7. 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
    We have prepared a temperature-sensitive Saccharomyces cerevisiae type 2A phosphatase (PP2A) mutant, pph21-102...
  8. Yasutis K, Vignali M, Ryder M, Tameire F, Dighe S, Fields S, et al. Zds2p regulates Swe1p-dependent polarized cell growth in Saccharomyces cerevisiae via a novel Cdc55p interaction domain. Mol Biol Cell. 2010;21:4373-86 pubmed publisher
    ..This negative regulation requires the CDC55 gene. Together these data indicate that the Cdc55p/Zds2p module has a function in the regulation of the Swe1p-dependent G2/M checkpoint. ..
  9. Bontron S, Jaquenoud M, Vaga S, Talarek N, Bodenmiller B, Aebersold R, et al. Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A. Cell Rep. 2013;3:16-22 pubmed publisher
    ..These results close a gap in our perception of and delineate a role for PP2A(Cdc55) in TORC1-/PKA-mediated regulation of quiescence and chronological life span. ..
  10. Ronne H, Carlberg M, Hu G, Nehlin J. Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth and bud morphogenesis. Mol Cell Biol. 1991;11:4876-84 pubmed
    We have cloned three genes for protein phosphatases in the yeast Saccharomyces cerevisiae. Two of the genes, PPH21 and PPH22, encode highly similar proteins that are homologs of the mammalian protein phosphatase 2A (PP2A), while the ..
  11. Rossio V, Yoshida S. Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitotic entry and mitotic exit in budding yeast. J Cell Biol. 2011;193:445-54 pubmed publisher
    ..Our analysis defines the long-sought molecular function for the zillion different screens family proteins and reveals the importance of the regulation of PP2A localization for proper mitotic progression. ..
  12. 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...
  13. Zheng Y, Jiang Y. The yeast phosphotyrosyl phosphatase activator is part of the Tap42-phosphatase complexes. Mol Biol Cell. 2005;16:2119-27 pubmed
  14. 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 Saccharomyces cerevisiae, Pph21 and Pph22 are the two catalytic subunits of type 2A phosphatase (PP2Ac), and Sit4 is a major form of 2A-like phosphatase...
  15. Petty E, Lafon A, Tomlinson S, Mendelsohn B, Pillus L. Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae. Genetics. 2016;203:1693-707 pubmed publisher
    ..These data highlight the potential significance of dynamic phosphorylation and dephosphorylation of these deeply conserved histone residues for cell viability. ..
  16. Sakumoto N, Matsuoka I, Mukai Y, Ogawa N, Kaneko Y, Harashima S. A series of double disruptants for protein phosphatase genes in Saccharomyces cerevisiae and their phenotypic analysis. Yeast. 2002;19:587-99 pubmed
    ..Four double disruptants exhibited synthetic phenotypes in addition to eight single ones: the pph21 pph22 double disruptant showed slow growth on complete medium, as did the sit4 and yvh1 single ones...
  17. Castermans D, Somers I, Kriel J, Louwet W, Wera S, Versele M, et al. Glucose-induced posttranslational activation of protein phosphatases PP2A and PP1 in yeast. Cell Res. 2012;22:1058-77 pubmed publisher
    ..Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent...
  18. Numamoto M, Sasano Y, Hirasaki M, Sugiyama M, Maekawa H, Harashima S. The protein phosphatase Siw14 controls caffeine-induced nuclear localization and phosphorylation of Gln3 via the type 2A protein phosphatases Pph21 and Pph22 in Saccharomyces cerevisiae. J Biochem. 2015;157:53-64 pubmed publisher
    ..although the nuclear localization of Gln3 is known to be induced by activation of the type 2A phosphatases (PP2As) Pph21 and Pph22, and the type 2A-related phosphatase Sit4...
  19. Garipler G, Mutlu N, Lack N, Dunn C. Deletion of conserved protein phosphatases reverses defects associated with mitochondrial DNA damage in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2014;111:1473-8 pubmed publisher
    ..Our work highlights the important role that nutrient-responsive signaling pathways can play in determining the response to mitochondrial dysfunction. ..
  20. Tate J, Georis I, Feller A, Dubois E, Cooper T. Rapamycin-induced Gln3 dephosphorylation is insufficient for nuclear localization: Sit4 and PP2A phosphatases are regulated and function differently. J Biol Chem. 2009;284:2522-34 pubmed publisher
    ..In contrast, Rap-induced nuclear Gln3 localization absolutely requires all four PP2A components (Pph21/22, Tpd3, Cdc55, and Rts1)...
  21. 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. ..
  22. Riedel C, Katis V, Katou Y, Mori S, Itoh T, Helmhart W, et al. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature. 2006;441:53-61 pubmed
    ..Our data are consistent with the notion that efficient cleavage of Rec8 requires phosphorylation of cohesin and that this is blocked by PP2A at meiosis I centromeres. ..
  23. Thai V, Dephoure N, Weiss A, Ferguson J, Leitao R, Gygi S, et al. Protein Kinase C Controls Binding of Igo/ENSA Proteins to Protein Phosphatase 2A in Budding Yeast. J Biol Chem. 2017;292:4925-4941 pubmed publisher
    ..Together, the data suggest that Pkc1 controls PP2ACdc55 by multiple overlapping mechanisms. ..
  24. Barbosa A, Pereira C, Osorio H, Moradas Ferreira P, Costa V. The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation. Cell Cycle. 2016;15:1620-30 pubmed publisher
    ..The overall results suggest that Hxk2p functions downstream of Sit4p in the control of cell cycle, mitochondrial function, oxidative stress resistance and chronological lifespan. ..
  25. Nakashima A, Maruki Y, Imamura Y, Kondo C, Kawamata T, Kawanishi I, et al. The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase. PLoS ONE. 2008;3:e2223 pubmed publisher
    ..The C-terminal polo-box domain of Cdc5 has an inhibitory role in nuclear translocation. Taken together, our results indicate a novel function of Tor in the regulation of cell cycle and proliferation. ..
  26. 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
    ..In the yeast Saccharomyces cerevisiae, the catalytic subunit of PP2A is encoded by two duplicated genes, PPH21 and PPH22. A third related gene, PPH3, also contributes some PP2A activity...
  27. 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
  28. Woodacre A, Lone M, Jablonowski D, Schneiter R, Giorgini F, Schaffrath R. A novel Sit4 phosphatase complex is involved in the response to ceramide stress in yeast. Oxid Med Cell Longev. 2013;2013:129645 pubmed publisher
    ..Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress. ..
  29. Tate J, Georis I, Dubois E, Cooper T. Distinct phosphatase requirements and GATA factor responses to nitrogen catabolite repression and rapamycin treatment in Saccharomyces cerevisiae. J Biol Chem. 2010;285:17880-95 pubmed publisher
    ..We previously demonstrated that the Sit4 and Pph21/22-Tpd3-Cdc55/Rts1 requirements for nuclear Gln3 localization differ...
  30. Moreno Torres M, Jaquenoud M, De Virgilio C. TORC1 controls G1-S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway. Nat Commun. 2015;6:8256 pubmed publisher
    ..Thus, Mpk1 and the greatwall kinase pathway serve TORC1 to coordinate the phosphorylation status of Sic1 and consequently START with nutrient availability. ..
  31. Mitchell D, Sprague G. The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae. Mol Cell Biol. 2001;21:488-500 pubmed
    ..Strains lacking both NCS1 and NOH1 were inviable and arrested as unbudded cells, implying that PTPA function is required for proper G(1) progression. ..
  32. Yaakov G, THORN K, Morgan D. Separase biosensor reveals that cohesin cleavage timing depends on phosphatase PP2A(Cdc55) regulation. Dev Cell. 2012;23:124-36 pubmed publisher
    ..Thus, separase acts directly on Scc1 and also indirectly, through inhibition of PP2A(Cdc55), to stimulate cohesin cleavage, providing a feedforward loop that may contribute to a robust and timely anaphase. ..
  33. Sun Y, Miao Y, Yamane Y, Zhang C, Shokat K, Takematsu H, et al. Orm protein phosphoregulation mediates transient sphingolipid biosynthesis response to heat stress via the Pkh-Ypk and Cdc55-PP2A pathways. Mol Biol Cell. 2012;23:2388-98 pubmed publisher
    ..We propose that this mechanism serves as the basis for how Orm phosphoregulation controls sphingolipid biosynthesis in response to stress in a kinetically coupled manner. ..
  34. Kuepfer L, Peter M, Sauer U, Stelling J. Ensemble modeling for analysis of cell signaling dynamics. Nat Biotechnol. 2007;25:1001-6 pubmed
    ..Beyond revising our picture of TOR signaling, we expect ensemble modeling to help elucidate other insufficiently characterized cellular circuits. ..
  35. McCourt P, Gallo Ebert C, Gonghong Y, Jiang Y, Nickels J. PP2A(Cdc55) regulates G1 cyclin stability. Cell Cycle. 2013;12:1201-10 pubmed publisher
    ..In sum, our results indicate that PP2A is absolutely required to maintain G1-S cyclin levels through modulating their phosphorylation status, an event necessary to properly transit through the cell cycle. ..
  36. Juanes M, Khoueiry R, Kupka T, Castro A, Mudrak I, Ogris E, et al. Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55) for timely mitotic progression. PLoS Genet. 2013;9:e1003575 pubmed publisher
    ..However, this conserved module is adapted to account for differences in the regulation of mitotic entry in different organisms. ..
  37. 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. ..
  38. 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
  39. Clotet J, Posas F, Hu G, Ronne H, Arino J. Role of protein phosphatase 2A in the control of glycogen metabolism in yeast. Eur J Biochem. 1995;229:207-14 pubmed
    The yeast homologues of mammalian protein phosphatase 2A (PP2A) are encoded by two genes, PPH21 and PPH22...
  40. Munoz I, Simon E, Casals N, Clotet J, Arino J. Identification of multicopy suppressors of cell cycle arrest at the G1-S transition in Saccharomyces cerevisiae. Yeast. 2003;20:157-69 pubmed
    ..The possible relationship between the known functions of these suppressor genes and the progress through the G(1)-S transition is discussed. ..
  41. Pracheil T, Thornton J, Liu Z. TORC2 signaling is antagonized by protein phosphatase 2A and the Far complex in Saccharomyces cerevisiae. Genetics. 2012;190:1325-39 pubmed publisher
    ..a member of the Far3-7-8-9-10-11 complex involved in pheromone-induced cell cycle arrest, interacts with Tpd3 and Pph21, conserved components of PP2A, and deletions of components of the Far3-7-8-9-10-11 complex and PP2A rescue growth ..
  42. Bohovych I, Kastora S, Christianson S, Topil D, Kim H, Fangman T, et al. Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses. Mol Cell Biol. 2016;36:2300-12 pubmed publisher