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2000
Volume 32, Issue 22
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

This review produces information about the role of protein phosphatase-6 () in various biological processes such as cell proliferation, cell cycle regulation, apoptosis, autophagy, cell migration and differentiation, and DNA damage repair. The issues of the participation of in the formation of tumor progression and the role of in the epigenetic regulation of the tumor process are covered. The article presents in detail the classification of mutations depending on the biological effects they have. It has been shown that various types of mutations in the gene can change the composition of the heterotrimeric complex, favoring some regulatory subunits over others, which promotes selective dephosphorylation of substrates to maintain cell viability and change their biological behavior. In particular, their proliferative activity is disrupted, leading to mitosis arrest at various cell cycle stages. An increase in the activity of Aurora A or a decrease in the activity of DNA-dependent protein kinase is considered the main molecular mechanism of tumor development associated with the inactivation of the pp6c protein. The article also discusses the topic of pharmacological modulation of activity. PP6 is a protein involved in many biological processes. In this regard, it is especially important to clarify the role of each PP6 holoenzyme and the molecular mechanisms that regulate the formation of the PP6 complex. Changes in the activity of this phosphatase can disrupt cell functioning.

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2025-09-02

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References

  1. CohenP.T.W. Novel protein serine/threonine phosphatases: Variety is the spice of life.Trends Biochem. Sci.199722724525110.1016/S0968‑0004(97)01060‑89255065
     [Google Scholar]
  2. MoorheadG.B.G. Trinkle-MulcahyL. Ulke-LeméeA. Emerging roles of nuclear protein phosphatases.Nat. Rev. Mol. Cell Biol.20078323424410.1038/nrm212617318227
     [Google Scholar]
  3. BilbroughT. PiemonteseE. SeitzO. Dissecting the role of protein phosphorylation: A chemical biology toolbox.Chem. Soc. Rev.202251135691573010.1039/D1CS00991E35726784
     [Google Scholar]
  4. JinJ. PawsonT. Modular evolution of phosphorylation-based signalling systems.Philos. Trans. R. Soc. Lond. B Biol. Sci.201236716022540255510.1098/rstb.2012.010622889906
     [Google Scholar]
  5. BarfordD. DasA.K. EgloffM.P. The structure and mechanism of protein phosphatases: insights into catalysis and regulation.Annu. Rev. Biophys. Biomol. Struct.199827113316410.1146/annurev.biophys.27.1.1339646865
     [Google Scholar]
  6. ShiY. Serine/threonine phosphatases: mechanism through structure.Cell2009139346848410.1016/j.cell.2009.10.00619879837
     [Google Scholar]
  7. BastanR. EskandariN. SabzghabaeeA.M. ManianM. Serine/Threonine phosphatases: classification, roles and pharmacological regulation.Int. J. Immunopathol. Pharmacol.201427447348410.1177/03946320140270040225572726
     [Google Scholar]
  8. PanJ. ZhouL. ZhangC. XuQ. SunY. Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal Transduct. Target. Ther.20227117710.1038/s41392‑022‑01038‑335665742
     [Google Scholar]
  9. GoldbergJ. HuangH. KwonY. GreengardP. NairnA.C. KuriyanJ. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1.Nature1995376654374575310.1038/376745a07651533
     [Google Scholar]
  10. TonksN.K. Protein tyrosine phosphatases: from genes, to function, to disease.Nat. Rev. Mol. Cell Biol.200671183384610.1038/nrm203917057753
     [Google Scholar]
  11. KamadaR. KudohF. ItoS. TaniI. JanairoJ.I.B. OmichinskiJ.G. SakaguchiK. Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors.Pharmacol. Ther.202021510762210.1016/j.pharmthera.2020.10762232650009
     [Google Scholar]
  12. HammondD. ZengK. EspertA. BastosR.N. BaronR.D. GrunebergU. BarrF.A. Melanoma-associated mutations in protein phosphatase 6 cause chromosome instability and DNA damage due to dysregulated Aurora-A.J. Cell Sci.2013126Pt 15jcs.12839710.1242/jcs.12839723729733
     [Google Scholar]
  13. ChoE. LouH.J. KuruvillaL. CalderwoodD.A. TurkB.E. PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK.Cell Rep.2021341310892810.1016/j.celrep.2021.10892833789117
     [Google Scholar]
  14. RusinS.F. AdamoM.E. KettenbachA.N. Identification of candidate casein kinase 2 substrates in mitosis by quantitative phosphoproteomics.Front. Cell Dev. Biol.201759710.3389/fcell.2017.0009729214152
     [Google Scholar]
  15. DouglasP. ZhongJ. YeR. MoorheadG.B.G. XuX. Lees-MillerS.P. Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX.Mol. Cell. Biol.20103061368138110.1128/MCB.00741‑0920065038
     [Google Scholar]
  16. WengrodJ. WangD. WeissS. ZhongH. OsmanI. GardnerL.B. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma.Sci. Signal.20158367ra2710.1126/scisignal.aaa089925759478
     [Google Scholar]
  17. YeJ. ShiH. ShenY. PengC. LiuY. LiC. DengK. GengJ. XuT. ZhuangY. ZhengB. TaoW. PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling.J. Immunol.201519441654166410.4049/jimmunol.140169225609840
     [Google Scholar]
  18. TanP. HeL. CuiJ. QianC. CaoX. LinM. ZhuQ. LiY. XingC. YuX. WangH.Y. WangR.F. Assembly of the WHIP-TRIM14-PPP6C mitochondrial complex promotes RIG-I-mediated antiviral signaling.Mol. Cell2017682293307.e510.1016/j.molcel.2017.09.03529053956
     [Google Scholar]
  19. BastiansH. KrebberH. VetrieD. HoheiselJ. LichterP. PonstinglH. JoosS. Localization of the novel serine/threonine protein phosphatase 6 gene (PPP6C) to human chromosome Xq22.3.Genomics199741229629710.1006/geno.1997.46409143513
     [Google Scholar]
  20. ZiembikM.A. BenderT.P. LarnerJ.M. BrautiganD.L. Functions of protein phosphatase-6 in NF-κB signaling and in lymphocytes.Biochem. Soc. Trans.201745369370110.1042/BST2016016928620030
     [Google Scholar]
  21. MaskinC.R. RamanR. HouvrasY. PPP6C, a serine-threonine phosphatase, regulates melanocyte differentiation and contributes to melanoma tumorigenesis through modulation of MITF activity.Sci. Rep.2022121557310.1038/s41598‑022‑08936‑035368039
     [Google Scholar]
  22. LyonsS.P. GreinerE.C. CresseyL.E. AdamoM.E. KettenbachA.N. Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation.Sci. Rep.20211112303110.1038/s41598‑021‑02456‑z34845248
     [Google Scholar]
  23. DopytalskaK. CiechanowiczP. WiszniewskiK. SzymańskaE. WaleckaI. The role of epigenetic factors in psoriasis.Int. J. Mol. Sci.20212217929410.3390/ijms2217929434502197
     [Google Scholar]
  24. WuN. LiuX. XuX. FanX. LiuM. LiX. ZhongQ. TangH. MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma.FEBS J.2011278122044205410.1111/j.1742‑4658.2011.08120.x21481188
     [Google Scholar]
  25. NagarajN. WisniewskiJ.R. GeigerT. CoxJ. KircherM. KelsoJ. PääboS. MannM. Deep proteome and transcriptome mapping of a human cancer cell line.Mol. Syst. Biol.20117154810.1038/msb.2011.8122068331
     [Google Scholar]
  26. CohenP. The origins of protein phosphorylation.Nat. Cell Biol.200245E127E13010.1038/ncb0502‑e12711988757
     [Google Scholar]
  27. YeelesJ.T.P. DeeganT.D. JanskaA. EarlyA. DiffleyJ.F.X. Regulated eukaryotic DNA replication origin firing with purified proteins.Nature2015519754443143510.1038/nature1428525739503
     [Google Scholar]
  28. ChengH.C. QiR.Z. PaudelH. ZhuH.J. Regulation and function of protein kinases and phosphatases.Enzyme Res.201120111310.4061/2011/79408922195276
     [Google Scholar]
  29. StefanssonB. BrautiganD.L. Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon.J. Biol. Chem.200628132226242263410.1074/jbc.M60177220016769727
     [Google Scholar]
  30. SharabiA. KasperI.R. TsokosG.C. The serine/threonine protein phosphatase 2A controls autoimmunity.Clin. Immunol.2018186384210.1016/j.clim.2017.07.01228736280
     [Google Scholar]
  31. ClarkA.R. OhlmeyerM. Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacol. Ther.201920118120110.1016/j.pharmthera.2019.05.01631158394
     [Google Scholar]
  32. FeldhammerM. UetaniN. Miranda-SaavedraD. TremblayM.L. PTP1B: A simple enzyme for a complex world.Crit. Rev. Biochem. Mol. Biol.201348543044510.3109/10409238.2013.81983023879520
     [Google Scholar]
  33. MizushimaN. LevineB. Autophagy in human diseases.N. Engl. J. Med.2020383161564157610.1056/NEJMra202277433053285
     [Google Scholar]
  34. WarfelN.A. NewtonA.C. Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): A new player in cell signaling.J. Biol. Chem.201228763610361610.1074/jbc.R111.31867522144674
     [Google Scholar]
  35. LammersT. PeschkeP. EhemannV. DebusJ. SlobodinB. LaviS. HuberP. Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity.Mol. Cancer2007616510.1186/1476‑4598‑6‑6517941990
     [Google Scholar]
  36. LuX. MaO. NguyenT.A. JonesS.N. OrenM. DonehowerL.A. The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop.Cancer Cell200712434235410.1016/j.ccr.2007.08.03317936559
     [Google Scholar]
  37. DickeyR.W. BobzinS.C. FaulknerD.J. BencsathF.A. AndrzejewskiD. Identification of okadaic acid from a Caribbean dinoflagellate, Prorocentrum concavum.Toxicon199028437137710.1016/0041‑0101(90)90074‑H2349579
     [Google Scholar]
  38. HaysteadT.A.J. SimA.T.R. CarlingD. HonnorR.C. TsukitaniY. CohenP. HardieD.G. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism.Nature19893376202788110.1038/337078a02562908
     [Google Scholar]
  39. WuergerL.T.D. BirkholzG. OberemmA. SiegH. BraeuningA. Proteomic analysis of hepatic effects of okadaic acid in HepaRG human liver cells.EXCLI J.2023221135114510.17179/excli2023‑6458
     [Google Scholar]
  40. TheobaldB. BonnessK. MusiyenkoA. AndrewsJ.F. UrbanG. HuangX. DeanN.M. HonkanenR.E. Suppression of Ser/Thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death.Mol. Cancer Res.201311884585510.1158/1541‑7786.MCR‑13‑003223671329
     [Google Scholar]
  41. ZhongJ. LiaoJ. LiuX. WangP. LiuJ. HouW. ZhuB. YaoL. WangJ. LiJ. StarkJ.M. XieY. XuX. Protein phosphatase PP6 is required for homology-directed repair of DNA double-strand breaks.Cell Cycle20111091411141910.4161/cc.10.9.1547921451261
     [Google Scholar]
  42. HayashiK. MomoiY. TanumaN. KishimotoA. OgohH. KatoH. SuzukiM. SakamotoY. InoueY. NomuraM. KiyonariH. SakayoriM. FukamachiK. KakugawaY. YamashitaY. ItoS. SatoI. SuzukiA. NishioM. SuganumaM. WatanabeT. ShimaH. Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA.Oncogene201534354647465510.1038/onc.2014.39825486434
     [Google Scholar]
  43. KatoH. KurosawaK. InoueY. TanumaN. MomoiY. HayashiK. OgohH. NomuraM. SakayoriM. KakugawaY. YamashitaY. MiuraK. MaemondoM. KatakuraR. ItoS. SatoM. SatoI. ChibaN. WatanabeT. ShimaH. Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis.Cancer Lett.2015365222322810.1016/j.canlet.2015.05.02226054846
     [Google Scholar]
  44. KishimotoK. KanazawaK. NomuraM. TanakaT. Shigemoto-KurodaT. FukuiK. MiuraK. KurosawaK. KawaiM. KatoH. TerasakiK. SakamotoY. YamashitaY. SatoI. TanumaN. TamaiK. KitabayashiI. MatsuuraK. WatanabeT. YasudaJ. TsujiH. ShimaH. PPP6C deficiency accelerates K-ras G12D -induced tongue carcinogenesis.Cancer Med.202110134451446410.1002/cam4.396234145991
     [Google Scholar]
  45. PalmieriG. ColombinoM. CasulaM. MancaA. MandalàM. CossuA. Italian melanoma intergroup (IMI). Molecular pathways in melanomagenesis: what we learned from next-generation sequencing approaches.Curr. Oncol. Rep.201820118610.1007/s11912‑018‑0733‑730218391
     [Google Scholar]
  46. KanazawaK. KishimotoK. NomuraM. KurosawaK. KatoH. InoueY. MiuraK. FukuiK. YamashitaY. SatoI. TsujiH. WatanabeT. TanakaT. YasudaJ. TanumaN. ShimaH. PPP6C haploinsufficiency accelerates UV-induced BRAF(V600E)-initiated melanomagenesis.Cancer Sci.202111262233224410.1111/cas.1489533743547
     [Google Scholar]
  47. LiM. ShuH.B. Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response.Protein Cell202011858459910.1007/s13238‑020‑00729‑332474700
     [Google Scholar]
  48. ComaiL. TanE.H. Haploid induction and genome instability.Trends Genet.2019351179180310.1016/j.tig.2019.07.00531421911
     [Google Scholar]
  49. DurutN. Mittelsten ScheidO. The role of noncoding RNAs in double-strand break repair.Front. Plant Sci.201910115510.3389/fpls.2019.0115531611891
     [Google Scholar]
  50. LavoieH. GagnonJ. TherrienM. ERK signalling: A master regulator of cell behaviour, life and fate.Nat. Rev. Mol. Cell Biol.2020211060763210.1038/s41580‑020‑0255‑732576977
     [Google Scholar]
  51. ZhangW. LiuH.T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells.Cell Res.200212191810.1038/sj.cr.729010511942415
     [Google Scholar]
  52. LiuY. ShepherdE.G. NelinL.D. MAPK phosphatases regulating the immune response.Nat. Rev. Immunol.20077320221210.1038/nri203517318231
     [Google Scholar]
  53. BurottoM. ChiouV.L. LeeJ.M. KohnE.C. The MAPK pathway across different malignancies: A new perspective.Cancer2014120223446345610.1002/cncr.2886424948110
     [Google Scholar]
  54. ShiY. ReddyB. ManleyJ.L. PP1/PP2A phosphatases are required for the second step of Pre-mRNA splicing and target specific snRNP proteins.Mol. Cell200623681982910.1016/j.molcel.2006.07.02216973434
     [Google Scholar]
  55. HendrikseC.S.E. TheelenP.M.M. van der PloegP. WestgeestH.M. BoereI.A. ThijsA.M.J. OttevangerP.B. van de StolpeA. LambrechtsS. BekkersR.L.M. PiekJ.M.J. The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis.Gynecol. Oncol.2023171839410.1016/j.ygyno.2023.01.03836841040
     [Google Scholar]
  56. SongY. BiZ. LiuY. QinF. WeiY. WeiX. Targeting RAS–RAF–MEK–ERK signaling pathway in human cancer: Current status in clinical trials.Genes Dis.2023101768810.1016/j.gendis.2022.05.00637013062
     [Google Scholar]
  57. FlahertyK.T. PuzanovI. KimK.B. RibasA. McArthurG.A. SosmanJ.A. O’DwyerP.J. LeeR.J. GrippoJ.F. NolopK. ChapmanP.B. Inhibition of mutated, activated BRAF in metastatic melanoma.N. Engl. J. Med.2010363980981910.1056/NEJMoa100201120818844
     [Google Scholar]
  58. GoldH.L. WengrodJ. de MieraE.V.S. WangD. FlemingN. SikkemaL. KirchhoffT. HochmanT. GoldbergJ.D. OsmanI. GardnerL.B. PP6C hotspot mutations in melanoma display sensitivity to Aurora kinase inhibition.Mol. Cancer Res.201412343343910.1158/1541‑7786.MCR‑13‑042224336958
     [Google Scholar]
  59. O’ConnorC.M. LeonardD. WiredjaD. AvelarR.A. WangZ. SchlatzerD. BrysonB. TokalaE. TaylorS.E. UpadhyayA. SangodkarJ. GingrasA.C. WestermarckJ. XuW. DiFeoA. BrautiganD.L. HaiderS. JacksonM. NarlaG. Inactivation of PP2A by a recurrent mutation drives resistance to MEK inhibitors.Oncogene202039370371710.1038/s41388‑019‑1012‑231541192
     [Google Scholar]
  60. KettenbachA.N. SchlosserK.A. LyonsS.P. NasaI. GuiJ. AdamoM.E. GerberS.A. Global assessment of its network dynamics reveals that the kinase Plk1 inhibits the phosphatase PP6 to promote Aurora A activity.Sci. Signal.201811530eaaq144110.1126/scisignal.aaq144129764989
     [Google Scholar]
  61. AfsharK. WernerM.E. TseY.C. GlotzerM. GönczyP. Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH-6 in one-cell stage C. elegans embryos.Development2010137223724710.1242/dev.04275420040490
     [Google Scholar]
  62. HiltonJ.F. ShapiroG.I. Aurora kinase inhibition as an anticancer strategy.J. Clin. Oncol.2014321575910.1200/JCO.2013.50.798824043748
     [Google Scholar]
  63. Puig-ButilleJ.A. VinyalsA. FerreresJ.R. AguileraP. CabréE. Tell-MartíG. MarcovalJ. MateoF. PalomeroL. BadenasC. PiulatsJ.M. MalvehyJ. PujanaM.A. PuigS. FabraÀ. AURKA overexpression is driven by FOXM1 and MAPK/ERK activation in melanoma cells harboring BRAF or NRAS mutations: Impact on melanoma prognosis and therapy.J. Invest. Dermatol.201713761297131010.1016/j.jid.2017.01.02128188776
     [Google Scholar]
  64. BoylanJ.M. SalomonA.R. TantravahiU. GruppusoP.A. Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit.Exp. Cell Res.2015335222423710.1016/j.yexcr.2015.05.00825999147
     [Google Scholar]
  65. ChawlaS. KunduD. RandhawaA. MondalA.K. The serine/threonine phosphatase DhSIT4 modulates cell cycle, salt tolerance and cell wall integrity in halo tolerant yeast Debaryomyces hansenii.Gene20176061910.1016/j.gene.2016.12.02228027965
     [Google Scholar]
  66. StefanssonB. BrautiganD.L. Protein phosphatase PP6 N terminal domain restricts G1 to S phase progression in human cancer cells.Cell Cycle20076111386139210.4161/cc.6.11.427617568194
     [Google Scholar]
  67. YanS. XuZ. LouF. ZhangL. KeF. BaiJ. LiuZ. LiuJ. WangH. ZhuH. SunY. CaiW. GaoY. SuB. LiQ. YangX. YuJ. LaiY. YuX.Z. ZhengY. ShenN. ChinY.E. WangH. NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis.Nat. Commun.201561765210.1038/ncomms865226138368
     [Google Scholar]
  68. LiX. HeS. MaB. Autophagy and autophagy-related proteins in cancer.Mol. Cancer20201911210.1186/s12943‑020‑1138‑431969156
     [Google Scholar]
  69. QuX. YuJ. BhagatG. FuruyaN. HibshooshH. TroxelA. RosenJ. EskelinenE.L. MizushimaN. OhsumiY. CattorettiG. LevineB. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.J. Clin. Invest.2003112121809182010.1172/JCI2003914638851
     [Google Scholar]
  70. MathewR. KarpC.M. BeaudoinB. VuongN. ChenG. ChenH.Y. BrayK. ReddyA. BhanotG. GelinasC. DiPaolaR.S. Karantza-WadsworthV. WhiteE. Autophagy suppresses tumorigenesis through elimination of p62.Cell200913761062107510.1016/j.cell.2009.03.04819524509
     [Google Scholar]
  71. FujiwaraN. ShibutaniS. SakaiY. WatanabeT. KitabayashiI. OshimaH. OshimaM. HoshidaH. AkadaR. UsuiT. OhamaT. SatoK. Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.Cancer Sci.2020111124371438010.1111/cas.1466232969571
     [Google Scholar]
  72. GarnettC.T. PalenaC. ChakarbortyM. TsangK.Y. SchlomJ. HodgeJ.W. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes.Cancer Res.200464217985799410.1158/0008‑5472.CAN‑04‑152515520206
     [Google Scholar]
  73. MoriM. BenotmaneM.A. VanhoveD. van HummelenP. Hooghe-PetersE.L. DesaintesC. Effect of ionizing radiation on gene expression in CD4+ T lymphocytes and in Jurkat cells: Unraveling novel pathways in radiation response.Cell. Mol. Life Sci.200461151955196410.1007/s00018‑004‑4147‑315341025
     [Google Scholar]
  74. MiJ. DziegielewskiJ. BolestaE. BrautiganD.L. LarnerJ.M. Activation of DNA-PK by ionizing radiation is mediated by protein phosphatase 6.PLoS One200942e439510.1371/journal.pone.000439519198648
     [Google Scholar]
  75. HanK.J. MikalayevaV. GerberS.A. KettenbachA.N. SkeberdisV.A. PrekerisR. Rab40c regulates focal adhesions and PP6 activity by controlling ANKRD28 ubiquitylation.Life Sci. Alliance202259e20210134610.26508/lsa.20210134635512830
     [Google Scholar]
  76. LevyC. KhaledM. FisherD.E. MITF: master regulator of melanocyte development and melanoma oncogene.Trends Mol. Med.200612940641410.1016/j.molmed.2006.07.00816899407
     [Google Scholar]
  77. GarrawayL.A. WidlundH.R. RubinM.A. GetzG. BergerA.J. RamaswamyS. BeroukhimR. MilnerD.A. GranterS.R. DuJ. LeeC. WagnerS.N. LiC. GolubT.R. RimmD.L. MeyersonM.L. FisherD.E. SellersW.R. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.Nature2005436704711712210.1038/nature0366416001072
     [Google Scholar]
  78. BertrandJ. SteingrimssonE. JouenneF. PailleretsB. LarueL. Melanoma risk and melanocyte biology.Acta Derm. Venereol.202010011adv0013910.2340/00015555‑349432346747
     [Google Scholar]
  79. SteingrímssonE. CopelandN.G. JenkinsN.A. Melanocytes and the microphthalmia transcription factor network.Annu. Rev. Genet.200438136541110.1146/annurev.genet.38.072902.09271715568981
     [Google Scholar]
  80. HossainS.M. EcclesM.R. Phenotype switching and the melanoma microenvironment; impact on immunotherapy and drug resistance.Int. J. Mol. Sci.2023242160110.3390/ijms2402160136675114
     [Google Scholar]
  81. SebergH.E. Van OtterlooE. CornellR.A. Beyond MITF : Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma.Pigment Cell Melanoma Res.201730545446610.1111/pcmr.1261128649789
     [Google Scholar]
  82. TravnickovaJ. WojciechowskaS. KhamsehA. GautierP. BrownD.V. LefevreT. BrombinA. EwingA. CapperA. SpitzerM. DilshatR. SempleC.A. MathersM.E. ListerJ.A. SteingrimssonE. VoetT. PontingC.P. PattonE.E. Zebrafish MITF-low melanoma subtype models reveal transcriptional subclusters and MITF-independent residual disease.Cancer Res.201979225769578410.1158/0008‑5472.CAN‑19‑003731582381
     [Google Scholar]
  83. LaussM. NsengimanaJ. StaafJ. Newton-BishopJ. JönssonG. Consensus of melanoma gene expression subtypes converges on biological entities.J. Invest. Dermatol.2016136122502250510.1016/j.jid.2016.05.11927345472
     [Google Scholar]
  84. SensiM. CataniM. CastellanoG. NicoliniG. AlciatoF. TragniG. De SantisG. BersaniI. AvanziG. TomassettiA. CanevariS. AnichiniA. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase.J. Invest. Dermatol.2011131122448245710.1038/jid.2011.21821796150
     [Google Scholar]
  85. MüllerJ. KrijgsmanO. TsoiJ. RobertL. HugoW. SongC. KongX. PossikP.A. Cornelissen-SteijgerP.D.M. FoppenM.H.G. KemperK. GodingC.R. McDermottU. BlankC. HaanenJ. GraeberT.G. RibasA. LoR.S. PeeperD.S. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma.Nat. Commun.201451571210.1038/ncomms671225502142
     [Google Scholar]
  86. McFarlandJ.M. HoZ.V. KugenerG. DempsterJ.M. MontgomeryP.G. BryanJ.G. Krill-BurgerJ.M. GreenT.M. VazquezF. BoehmJ.S. GolubT.R. HahnW.C. RootD.E. TsherniakA. Improved estimation of cancer dependencies from large-scale RNAi screens using model-based normalization and data integration.Nat. Commun.201891461010.1038/s41467‑018‑06916‑530389920
     [Google Scholar]
  87. BouwmeesterT. BauchA. RuffnerH. AngrandP.O. BergaminiG. CroughtonK. CruciatC. EberhardD. GagneurJ. GhidelliS. HopfC. HuhseB. ManganoR. MichonA.M. SchirleM. SchleglJ. SchwabM. SteinM.A. BauerA. CasariG. DrewesG. GavinA.C. JacksonD.B. JobertyG. NeubauerG. RickJ. KusterB. Superti-FurgaG. A physical and functional map of the human TNF-α/NF-κB signal transduction pathway.Nat. Cell Biol.2004629710510.1038/ncb108614743216
     [Google Scholar]
  88. KajiharaR. FukushigeS. ShiodaN. TanabeK. FukunagaK. InuiS. CaMKII phosphorylates serine 10 of p27 and confers apoptosis resistance to HeLa cells.Biochem. Biophys. Res. Commun.2010401335035510.1016/j.bbrc.2010.09.05120851109
     [Google Scholar]
  89. BroglieP. MatsumotoK. AkiraS. BrautiganD.L. Ninomiya-TsujiJ. Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway.J. Biol. Chem.201028542333233910.1074/jbc.M109.09052219955178
     [Google Scholar]
  90. PrickettT.D. Ninomiya-TsujiJ. BroglieP. Muratore-SchroederT.L. ShabanowitzJ. HuntD.F. BrautiganD.L. TAB4 stimulates TAK1-TAB1 phosphorylation and binds polyubiquitin to direct signaling to NF-kappaB.J. Biol. Chem.200828328192451925410.1074/jbc.M80094320018456659
     [Google Scholar]
  91. KhanD. BednerP. MüllerJ. LülsbergF. HenningL. PrinzM. SteinhäuserC. MuhammadS. TGF-β activated kinase 1 (TAK1) is activated in microglia after experimental epilepsy and contributes to epileptogenesis.Mol. Neurobiol.20236063413342210.1007/s12035‑023‑03290‑236862288
     [Google Scholar]
  92. KajinoT. RenH. IemuraS. NatsumeT. StefanssonB. BrautiganD.L. MatsumotoK. Ninomiya-TsujiJ. Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway.J. Biol. Chem.200628152398913989610.1074/jbc.M60815520017079228
     [Google Scholar]
  93. VincentA. BerthelE. DacheuxE. MagnardC. VeneziaN.L.D. BRCA1 affects protein phosphatase 6 signalling through its interaction with ANKRD28.Biochem. J.2016473794996010.1042/BJ2015079727026398
     [Google Scholar]
  94. HodisE. WatsonI.R. KryukovG.V. AroldS.T. ImielinskiM. TheurillatJ.P. NickersonE. AuclairD. LiL. PlaceC. DiCaraD. RamosA.H. LawrenceM.S. CibulskisK. SivachenkoA. VoetD. SaksenaG. StranskyN. OnofrioR.C. WincklerW. ArdlieK. WagleN. WargoJ. ChongK. MortonD.L. Stemke-HaleK. ChenG. NobleM. MeyersonM. LadburyJ.E. DaviesM.A. GershenwaldJ.E. WagnerS.N. HoonD.S.B. SchadendorfD. LanderE.S. GabrielS.B. GetzG. GarrawayL.A. ChinL. A landscape of driver mutations in melanoma.Cell2012150225126310.1016/j.cell.2012.06.02422817889
     [Google Scholar]
  95. WandziochE. PuseyM. WerdaA. BailS. BhaskarA. NestorM. YangJ.J. RiceL.M. PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.Cancer Res.201474164295430510.1158/0008‑5472.CAN‑13‑313024928782
     [Google Scholar]
  96. SatoN. FukushimaN. MaitraA. Iacobuzio-DonahueC.A. van HeekN.T. CameronJ.L. YeoC.J. HrubanR.H. GogginsM. Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas.Am. J. Pathol.2004164390391410.1016/S0002‑9440(10)63178‑114982844
     [Google Scholar]
  97. ShenY. WangY. ShengK. FeiX. GuoQ. LarnerJ. KongX. QiuY. MiJ. Serine/threonine protein phosphatase 6 modulates the radiation sensitivity of glioblastoma.Cell Death Dis.2011212e24110.1038/cddis.2011.12622158480
     [Google Scholar]
  98. NaguroI. UmedaT. KobayashiY. MaruyamaJ. HattoriK. ShimizuY. KataokaK. Kim-MitsuyamaS. UchidaS. VandewalleA. NoguchiT. NishitohH. MatsuzawaA. TakedaK. IchijoH. ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney.Nat. Commun.201231128510.1038/ncomms228323250415
     [Google Scholar]
  99. WatanabeK. UmedaT. NiwaK. NaguroI. IchijoH. PP6-ASK3 Module coordinates the bidirectional cell volume regulation under osmotic stress.Cell Rep.201822112809281710.1016/j.celrep.2018.02.04529539411
     [Google Scholar]
  100. PrickettT.D. BrautiganD.L. The alpha4 regulatory subunit exerts opposing allosteric effects on protein phosphatases PP6 and PP2A.J. Biol. Chem.200628141305033051110.1074/jbc.M60105420016895907
     [Google Scholar]
  101. LeeK.K. YoneharaS. Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST).J. Biol. Chem.200227714123511235810.1074/jbc.M10813820011805089
     [Google Scholar]
  102. PraskovaM. KhoklatchevA. Ortiz-VegaS. AvruchJ. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.Biochem. J.2004381245346210.1042/BJ2004002515109305
     [Google Scholar]
  103. HataY. TimalsinaS. MaimaitiS. Okadaic Acid: A tool to study the hippo pathway.Mar. Drugs201311389690210.3390/md1103089623493077
     [Google Scholar]
  104. HanejiT. HirashimaK. TeramachiJ. MorimotoH. Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells.Int. J. Oncol.20134261904191010.3892/ijo.2013.191123591640
     [Google Scholar]
  105. ZeguraB. An overview of the mechanisms of microcystin-lr genotoxicity and potential carcinogenicity.Mini Rev. Med. Chem.201616131042106210.2174/138955751666616030814154926951459
     [Google Scholar]
  106. Pozuelo-RubioM. LeslieN.R. MurphyJ. MackintoshC. Mechanism of activation of PKB/Akt by the protein phosphatase inhibitor Calyculin A.Cell Biochem Biophys201058314715610.1007/s12013‑010‑9101‑4
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673310356240630103257
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Functional Role of Protein Phosphatase-6 (PPP6c): Regulation of Expression and Modulation of Activity
Curr. Med. Chem. 32, 4481 (2025); https://doi.org/10.2174/0109298673310356240630103257
/content/journals/cmc/10.2174/0109298673310356240630103257
/content/journals/cmc/10.2174/0109298673310356240630103257
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  • Article Type:     Review Article
Keyword(s): aurora; expression; holoenzyme; modulation; phosphatase-6; ppp6c; Protein

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