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Nuclear Phosphoinositides: Location, Regulation and Function

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Phosphoinositides II: The Diverse Biological Functions

Part of the book series: Subcellular Biochemistry ((SCBI,volume 59))

Abstract

Lipid signalling in human disease is an important field of investigation and stems from the fact that phosphoinositide signalling has been implicated in the control of nearly all the important cellular pathways including metabolism, cell cycle control, membrane trafficking, apoptosis and neuronal conduction. A distinct nuclear inositide signalling metabolism has been identified, thus defining a new role for inositides in the nucleus, which are now considered essential co-factors for several nuclear processes, including DNA repair, transcription regulation, and RNA dynamics. Deregulation of phoshoinositide metabolism within the nuclear compartment may contribute to disease progression in several disorders, such as chronic inflammation, cancer, metabolic, and degenerative syndromes. In order to utilize these very druggable pathways for human benefit there is a need to identify how nuclear inositides are regulated specifically within this compartment and what downstream nuclear effectors process and integrate inositide signalling cascades in order to specifically control nuclear function. Here we describe some of the facets of nuclear inositide metabolism with a focus on their relationship to cell cycle control and differentiation.

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References

  • Ahn JY, Ye K (2005) PIKE GTPase signaling and function. Int J Biol Sci 1:44–50

    PubMed  CAS  Google Scholar 

  • Ahn JY Rong R, Liu X, Ye K (2004) PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus. EMBO J 23:3995–4006

    PubMed  CAS  Google Scholar 

  • Alvarez-Venegas R, Pien S, Sadder M, Witmer X, Grossniklaus U, Avramova Z (2003) ATX-1, an Arabidopsis homolog of trithorax, activates flower homeotic genes. Curr Biol 13:627–637

    PubMed  CAS  Google Scholar 

  • Alvarez-Venegas R, Sadder M, Hlavacka A, Baluska F, Xia Y, Lu G, Firsov A, Sarath G, Moriyama H, Dubrovsky JG, Avramova Z (2006) The Arabidopsis homolog of trithorax, ATX1, binds phosphatidylinositol 5-phosphate, and the two regulate a common set of target genes. Proc Natl Acad Sci U S A 103:6049–6054

    PubMed  CAS  Google Scholar 

  • Ananthanarayanan B, Ni Q, Zhang J (2005) Signal propagation from membrane messengers to nuclear effectors revealed by reporters of phosphoinositide dynamics and Akt activity. Proc Natl Acad Sci U S A 102:15081–15086

    PubMed  CAS  Google Scholar 

  • Avazeri N, Courtot AM, Pesty A, Duquenne C, Lefevre B (2000) Cytoplasmic and nuclear phospholipase C-beta 1 relocation: role in resumption of meiosis in the mouse oocyte. Mol Biol Cell 11:4369–4380

    PubMed  CAS  Google Scholar 

  • Bacqueville D, Deleris P, Mendre C, Pieraggi MT, Chap H, Guillon G, Perret B, Breton-Douillon M (2001) Characterization of a G protein-activated phosphoinositide 3-kinase in vascular smooth muscle cell nuclei. J Biol Chem 276:22170–22176

    PubMed  CAS  Google Scholar 

  • Bading H, Hardingham GE, Johnson CM, Chawla S (1997) Gene regulation by nuclear and cytoplasmic calcium signals. Biochem Biophys Res Commun 236:541–543

    PubMed  CAS  Google Scholar 

  • Balla A, Balla T (2006) Phosphatidylinositol 4-kinases: old enzymes with emerging functions. Trends Cell Biol 16:351–361

    PubMed  CAS  Google Scholar 

  • Banfic H, Zizak M, Divecha N, Irvine RF (1993) Nuclear diacylglycerol is increased during cell proliferation in vivo. Biochem J 290(Pt 3):633–636

    PubMed  CAS  Google Scholar 

  • Bavelloni A, Faenza I, Cioffi G, Piazzi M, Parisi D, Matic I, Maraldi NM, Cocco L (2006) Proteomic-based analysis of nuclear signaling: PLCbeta1 affects the expression of the splicing factor SRp20 in Friend erythroleukemia cells. Proteomics 6:5725–5734

    PubMed  CAS  Google Scholar 

  • Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51:189–199

    PubMed  CAS  Google Scholar 

  • Bertagnolo V, Brugnoli F, Marchisio M, Capitani S (2004) Inositide-modifying enzymes: a cooperative role in regulating nuclear morphology during differentiation of myeloid cells. J Biol Regul Homeost Agents 18:381–386

    PubMed  CAS  Google Scholar 

  • Boronenkov IV, Loijens JC, Umeda M, Anderson RA (1998) Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol Biol Cell 9:3547–3560

    PubMed  CAS  Google Scholar 

  • Bultsma Y, Keune WJ, Divecha N (2010) PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. Biochem J 430:223–235

    PubMed  CAS  Google Scholar 

  • Cenciarelli C, De Santa F, Puri PL, Mattei E, Ricci L, Bucci F, Felsani A, Caruso M (1999) Critical role played by cyclin D3 in the MyoD-mediated arrest of cell cycle during myoblast differentiation. Mol Cell Biol 19:5203–5217

    PubMed  CAS  Google Scholar 

  • Cenni V, Bertacchini J, Beretti F, Lattanzi G, Bavelloni A, Riccio M, Ruzzene M, Marin O, Arrigoni G, Parnaik V, Wehnert M, Maraldi NM, De Pol A, Cocco L, Marmiroli S (2008) Lamin A Ser404 is a nuclear target of Akt phosphorylation in C2C12 cells. J Proteome Res 7:4727–4735

    PubMed  CAS  Google Scholar 

  • Cheng MK, Shearn A (2004) The direct interaction between ASH2, a Drosophila trithorax group protein, and SKTL, a nuclear phosphatidylinositol 4-phosphate 5-kinase, implies a role for phosphatidylinositol 4,5-bisphosphate in maintaining transcriptionally active chromatin. Genetics 167:1213–1223

    PubMed  CAS  Google Scholar 

  • Chu CY, Lim RW (2000) Involvement of p27(kip1) and cyclin D3 in the regulation of cdk2 activity during skeletal muscle differentiation. Biochim Biophys Acta 1497:175–185

    PubMed  CAS  Google Scholar 

  • Ciruela A, Hinchliffe KA, Divecha N, Irvine RF (2000) Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7. Biochem J 346(Pt 3):587–591

    PubMed  CAS  Google Scholar 

  • Cocco L, Gilmour RS, Ognibene A, Letcher AJ, Manzoli FA, Irvine RF (1987) Synthesis of polyphosphoinositides in nuclei of Friend cells. Evidence for polyphosphoinositide metabolism inside the nucleus which changes with cell differentiation. Biochem J 248:765–770

    PubMed  CAS  Google Scholar 

  • Cocco L, Martelli AM, Gilmour RS, Ognibene A, Manzoli FA, Irvine RF (1988) Rapid changes in phospholipid metabolism in the nuclei of Swiss 3T3 cells induced by treatment of the cells with insulin-like growth factor I. Biochem Biophys Res Commun 154:1266–1272

    PubMed  CAS  Google Scholar 

  • Cocco L, Martelli AM, Gilmour RS, Ognibene A, Manzoli FA, Irvine RF (1989) Changes in nuclear inositol phospholipids induced in intact cells by insulin-like growth factor I. Biochem Biophys Res Commun 159:720–725

    PubMed  CAS  Google Scholar 

  • Cocco L, Faenza I, Follo MY, Billi AM, Ramazzotti G, Papa V, Martelli AM, Manzoli L (2009) Nuclear inositides: PI-PLC signaling in cell growth, differentiation and pathology. Adv Enzyme Regul 49:2–10

    PubMed  CAS  Google Scholar 

  • Collins SJ (1987) The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood 70:1233–1244

    PubMed  CAS  Google Scholar 

  • Coronas S, Lagarrigue F, Ramel D, Chicanne G, Delsol G, Payrastre B, Tronchere H (2008) Elevated levels of PtdIns5P in NPM-ALK transformed cells: implication of PIKfyve. Biochem Biophys Res Commun 372:351–355

    PubMed  CAS  Google Scholar 

  • Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Kohler G, Wijermans P, Jones PA, Lubbert M (2002) Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2¢-deoxycytidine (decitabine) treatment. Blood 100:2957–2964

    PubMed  CAS  Google Scholar 

  • Deleris P, Gayral S, Breton-Douillon M (2006) Nuclear Ptdlns(3,4,5)P 3 signaling: an ongoing story. J Cell Biochem 98:469–485

    PubMed  CAS  Google Scholar 

  • Didichenko SA, Thelen M (2001) Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles. J Biol Chem 276:48135–48142

    PubMed  CAS  Google Scholar 

  • Divecha N, Banfic H, Irvine RF (1991) The polyphosphoinositide cycle exists in the nuclei of Swiss 3T3 cells under the control of a receptor (for IGF-I) in the plasma membrane, and stimulation of the cycle increases nuclear diacylglycerol and apparently induces translocation of protein kinase C to the nucleus. EMBO J 10:3207–3214

    PubMed  CAS  Google Scholar 

  • Divecha N, Rhee SG, Letcher AJ, Irvine RF (1993) Phosphoinositide signalling enzymes in rat liver nuclei: phosphoinositidase C isoform beta 1 is specifically, but not predominantly, located in the nucleus. Biochem J 289(Pt 3):617–620

    PubMed  CAS  Google Scholar 

  • Divecha N, Letcher AJ, Banfic HH, Rhee SG, Irvine RF (1995) Changes in the components of a nuclear inositide cycle during differentiation in murine erythroleukaemia cells. Biochem J 312(Pt 1):63–67

    PubMed  CAS  Google Scholar 

  • Divecha N, Roefs M, Los A, Halstead J, Bannister A, D’Santos C (2002) Type I PIPkinases interact with and are regulated by the retinoblastoma susceptibility gene product-pRB. Curr Biol 12:582–587

    PubMed  CAS  Google Scholar 

  • Evangelisti C, Riccio M, Faenza I, Zini N, Hozumi Y, Goto K, Cocco L, Martelli AM (2006) Subnuclear localization and differentiation-dependent increased expression of DGK-zeta in C2C12 mouse myoblasts. J Cell Physiol 209:370–378

    PubMed  CAS  Google Scholar 

  • Evangelisti C, Tazzari PL, Riccio M, Fiume R, Hozumi Y, Fala F, Goto K, Manzoli L, Cocco L, Martelli AM (2007) Nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts. FASEB J 21:3297–3307

    PubMed  CAS  Google Scholar 

  • Faenza I, Matteucci A, Manzoli L, Billi AM, Aluigi M, Peruzzi D, Vitale M, Castorina S, Suh PG, Cocco L (2000) A role for nuclear phospholipase Cbeta 1 in cell cycle control. J Biol Chem 275:30520–30524

    PubMed  CAS  Google Scholar 

  • Faenza I, Matteucci A, Bavelloni A, Marmiroli S, Martelli AM, Gilmour RS, Suh PG, Manzoli L, Cocco L (2002) Nuclear PLCbeta(1) acts as a negative regulator of p45/NF-E2 expression levels in friend erythroleukemia cells. Biochim Biophys Acta 1589:305–310

    PubMed  CAS  Google Scholar 

  • Faenza I, Bavelloni A, Fiume R, Lattanzi G, Maraldi NM, Gilmour RS, Martelli AM, Suh PG, Billi AM, Cocco L (2003) Up-regulation of nuclear PLCbeta1 in myogenic differentiation. J Cell Physiol 195:446–452

    PubMed  CAS  Google Scholar 

  • Faenza I, Bavelloni A, Fiume R, Santi P, Martelli AM, Maria Billi A, Lo Vasco VR, Manzoli L, Cocco L (2004) Expression of phospholipase C beta family isoenzymes in C2C12 myoblasts during terminal differentiation. J Cell Physiol 200:291–296

    PubMed  CAS  Google Scholar 

  • Faenza I, Billi AM, Follo MY, Fiume R, Martelli AM, Cocco L, Manzoli L (2005) Nuclear phospholipase C signaling through type 1 IGF receptor and its involvement in cell growth and differentiation. Anticancer Res 25:2039–2041

    PubMed  CAS  Google Scholar 

  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10:223–232

    PubMed  CAS  Google Scholar 

  • Fiume R, Faenza I, Matteucci A, Astolfi A, Vitale M, Martelli AM, Cocco L (2005) Nuclear phospholipase C beta1 (PLCbeta1) affects CD24 expression in murine erythroleukemia cells. J Biol Chem 280:24221–24226

    PubMed  CAS  Google Scholar 

  • Fiume R, Ramazzotti G, Teti G, Chiarini F, Faenza I, Mazzotti G, Billi AM, Cocco L (2009) Involvement of nuclear PLC{beta}1 in lamin B1 phosphorylation and G2/M cell cycle progression. FASEB J 23:957–966

    PubMed  CAS  Google Scholar 

  • Follo MY, Bosi C, Finelli C, Fiume R, Faenza I, Ramazzotti G, Gaboardi GC, Manzoli L, Cocco L (2006) Real-time PCR as a tool for quantitative analysis of PI-PLCbeta1 gene expression in myelodysplastic syndrome. Int J Mol Med 18:267–271

    PubMed  CAS  Google Scholar 

  • Follo MY, Finelli C, Bosi C, Martinelli G, Mongiorgi S, Baccarani M, Manzoli L, Blalock WL, Martelli AM, Cocco L (2008) PI-PLCbeta-1 and activated akt levels are linked to azacitidine responsiveness in high-risk myelodysplastic syndromes. Leukemia 22:198–200

    PubMed  CAS  Google Scholar 

  • Follo MY, Finelli C, Clissa C, Mongiorgi S, Bosi C, Martinelli G, Baccarani M, Manzoli L, Martelli AM, Cocco L (2009a) Phosphoinositide-phospholipase C beta1 mono-allelic deletion is associated with myelodysplastic syndromes evolution into acute myeloid leukemia. J Clin Oncol 27:782–790

    Google Scholar 

  • Follo MY, Finelli C, Mongiorgi S, Clissa C, Bosi C, Testoni N, Chiarini F, Ramazzotti G, Baccarani M, Martelli AM, Manzoli L, Martinelli G, Cocco L (2009b) Reduction of phosphoinositide-phospholipase C beta1 methylation predicts the responsiveness to azacitidine in high-risk MDS. Proc Natl Acad Sci U S A 106:16811–16816

    Google Scholar 

  • Follo MY, Finelli C, Mongiorgi S, Clissa C, Chiarini F, Ramazzotti G, Paolini S, Martinelli G, Martelli AM, Cocco L (2011) Synergistic induction of PI-PLCbeta1 signaling by azacitidine and valproic acid in high-risk myelodysplastic syndromes. Leukemia 25(2):271–280

    Google Scholar 

  • Frederick JP, Mattiske D, Wofford JA, Megosh LC, Drake LY, Chiou ST, Hogan BL, York JD (2005) An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. Proc Natl Acad Sci U S A 102:8454–8459

    PubMed  CAS  Google Scholar 

  • Gokmen-Polar Y, Fields AP (1998) Mapping of a molecular determinant for protein kinase C betaII isozyme function. J Biol Chem 273:20261–20266

    PubMed  CAS  Google Scholar 

  • Gomes DA, Rodrigues MA, Leite MF, Gomez MV, Varnai P, Balla T, Bennett AM, Nathanson MH (2008) c-Met must translocate to the nucleus to initiate calcium signals. J Biol Chem 283:4344–4351

    PubMed  CAS  Google Scholar 

  • Gonzales ML, Mellman DL, Anderson RA (2008) CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs. J Biol Chem 283:12665–12673

    PubMed  CAS  Google Scholar 

  • Goss VL, Hocevar BA, Thompson LJ, Stratton CA, Burns DJ, Fields AP (1994) Identification of nuclear beta II protein kinase C as a mitotic lamin kinase. J Biol Chem 269:19074–19080

    PubMed  CAS  Google Scholar 

  • Gozani O, Karuman P, Jones DR, Ivanov D, Cha J, Lugovskoy AA, Baird CL, Zhu H, Field SJ, Lessnick SL, Villasenor J, Mehrotra B, Chen J, Rao VR, Brugge JS, Ferguson CG, Payrastre B, Myszka DG, Cantley LC, Wagner G, Divecha N, Prestwich GD, Yuan J (2003) The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell 114:99–111

    PubMed  CAS  Google Scholar 

  • Greenberg P, Cox C, Lebeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088

    PubMed  CAS  Google Scholar 

  • Hardingham GE, Chawla S, Johnson CM, Bading H (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385:260–265

    PubMed  CAS  Google Scholar 

  • Hocevar BA, Fields AP (1991) Selective translocation of beta II-protein kinase C to the nucleus of human promyelocytic (HL60) leukemia cells. J Biol Chem 266:28–33

    PubMed  CAS  Google Scholar 

  • Hocevar BA, Burns DJ, Fields AP (1993) Identification of protein kinase C (PKC) phosphorylation sites on human lamin B. Potential role of PKC in nuclear lamina structural dynamics. J Biol Chem 268:7545–7552

    PubMed  CAS  Google Scholar 

  • Humbert JP, Matter N, Artault JC, Koppler P, Malviya AN (1996) Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate. Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes. J Biol Chem 271:478–485

    PubMed  CAS  Google Scholar 

  • Irvine RF (2005) Inositide evolution—towards turtle domination? J Physiol 566:295–300

    PubMed  CAS  Google Scholar 

  • Jones DR, Bultsma Y, Keune WJ, Halstead JR, Elouarrat D, Mohammed S, Heck AJ, D’Santos CS, Divecha N (2006) Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for PIP4Kbeta. Mol Cell 23:685–695

    PubMed  CAS  Google Scholar 

  • Kiess M, Gill RM, Hamel PA (1995) Expression of the positive regulator of cell cycle progression, cyclin D3, is induced during differentiation of myoblasts into quiescent myotubes. Oncogene 10:159–166

    PubMed  CAS  Google Scholar 

  • Kumar V, Jong YJ, O’Malley KL (2008) Activated nuclear metabotropic glutamate receptor mGlu5 couples to nuclear Gq/11 proteins to generate inositol 1,4,5-trisphosphate-mediated nuclear Ca2+ release. J Biol Chem 283:14072–14083

    PubMed  CAS  Google Scholar 

  • Lassar AB, Skapek SX, Novitch B (1994) Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. Curr Opin Cell Biol 6:788–794

    PubMed  CAS  Google Scholar 

  • Lee YS, Mulugu S, York JD, O’Shea EK (2007) Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science 316:109–112

    PubMed  CAS  Google Scholar 

  • Lemmon MA (2003) Phosphoinositide recognition domains. Traffic 4:201–213

    PubMed  CAS  Google Scholar 

  • Lewis AE, Sommer L, Arntzen MO, Strahm Y, Morrice NA, Divecha N, D’Santos CS (2011) Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Mol Cell Proteomics 10(2):M110.003376

    Google Scholar 

  • Lindsay Y, McCoull D, Davidson L, Leslie NR, Fairservice A, Gray A, Lucocq J, Downes CP (2006) Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. J Cell Sci 119:5160–5168

    PubMed  CAS  Google Scholar 

  • Loijens JC, Boronenkov IV, Parker GJ, Anderson RA (1996) The phosphatidylinositol 4-phosphate 5-kinase family. Adv Enzyme Regul 36:115–140

    PubMed  CAS  Google Scholar 

  • Los AP, Vinke FP, De Widt J, Topham MK, Van Blitterswijk WJ, Divecha N (2006) The retinoblastoma family proteins bind to and activate diacylglycerol kinase zeta. J Biol Chem 281:858–866

    PubMed  CAS  Google Scholar 

  • Lukinovic-Skudar V, Donlagic L, Banfic H, Visnjic D (2005) Nuclear phospholipase C-beta1b activation during G2/M and late G1 phase in nocodazole-synchronized HL-60 cells. Biochim Biophys Acta 1733:148–156

    PubMed  CAS  Google Scholar 

  • Lukinovic-Skudar V, Matkovic K, Banfic H, Visnjic D (2007) Two waves of the nuclear phospholipase C activity in serum-stimulated HL-60 cells during G(1) phase of the cell cycle. Biochim Biophys Acta 1771:514–521

    PubMed  CAS  Google Scholar 

  • Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M (2007) Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 25:3503–3510

    PubMed  Google Scholar 

  • Malviya AN, Rogue P, Vincendon G (1990) Stereospecific inositol 1,4,5-[32P]trisphosphate binding to isolated rat liver nuclei: evidence for inositol trisphosphate receptor-mediated calcium release from the nucleus. Proc Natl Acad Sci U S A 87:9270–9274

    PubMed  CAS  Google Scholar 

  • Manzoli FA, Martelli AM, Capitani S, Maraldi NM, Rizzoli R, Barnabei O, Cocco L (1989) Nuclear polyphosphoinositides during cell growth and differentiation. Adv Enzyme Regul 28:25–34

    PubMed  CAS  Google Scholar 

  • Manzoli L, Billi AM, Rubbini S, Bavelloni A, Faenza I, Gilmour RS, Rhee SG, Cocco L (1997) Essential role for nuclear phospholipase C beta1 in insulin-like growth factor I-induced mitogenesis. Cancer Res 57:2137–2139

    PubMed  CAS  Google Scholar 

  • Marmiroli S, Bertacchini J, Beretti F, Cenni V, Guida M, De Pol A, Maraldi NM, Lattanzi G (2009) A-type lamins and signaling: the PI 3-kinase/Akt pathway moves forward. J Cell Physiol 220:553–561

    PubMed  CAS  Google Scholar 

  • Martelli AM, Gilmour RS, Neri LM, Manzoli L, Corps AN, Cocco L (1991) Mitogen-stimulated events in nuclei of Swiss 3T3 cells. Evidence for a direct link between changes of inositol lipids, protein kinase C requirement and the onset of DNA synthesis. FEBS Lett 283:243–246

    PubMed  CAS  Google Scholar 

  • Martelli AM, Gilmour RS, Bertagnolo V, Neri LM, Manzoli L, Cocco L (1992) Nuclear localization and signalling activity of phosphoinositidase C beta in Swiss 3T3 cells. Nature 358:242–245

    PubMed  CAS  Google Scholar 

  • Martelli AM, Billi AM, Gilmour RS, Neri LM, Manzoli L, Ognibene A, Cocco L (1994) Phosphoinositide signaling in nuclei of Friend cells: phospholipase C beta down-regulation is related to cell differentiation. Cancer Res 54:2536–2540

    PubMed  CAS  Google Scholar 

  • Matkovic K, Brugnoli F, Bertagnolo V, Banfic H, Visnjic D (2006) The role of the nuclear Akt activation and Akt inhibitors in all-trans-retinoic acid-differentiated HL-60 cells. Leukemia 20:941–951

    PubMed  CAS  Google Scholar 

  • Matsuyama R, Takada I, Yokoyama A, Fujiyma-Nakamura S, Tsuji N, Kitagawa H, Fujiki R, Kim M, Kouzu-Fujita M, Yano T, Kato S (2010) Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor alpha through histone deacetylase 1. J Biol Chem 285:18166–18176

    PubMed  CAS  Google Scholar 

  • Matteucci A, Faenza I, Gilmour RS, Manzoli L, Billi AM, Peruzzi D, Bavelloni A, Rhee SG, Cocco L (1998) Nuclear but not cytoplasmic phospholipase C beta 1 inhibits differentiation of erythroleukemia cells. Cancer Res 58:5057–5060

    PubMed  CAS  Google Scholar 

  • McCrea HJ, De Camilli P (2009) Mutations in phosphoinositide metabolizing enzymes and human disease. Physiology (Bethesda) 24:8–16

    CAS  Google Scholar 

  • Mellman DL, Gonzales ML, Song C, Barlow CA, Wang P, Kendziorski C, Anderson RA (2008) A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature 451:1013–1017

    PubMed  CAS  Google Scholar 

  • Metjian A, Roll RL, Ma AD, Abrams CS (1999) Agonists cause nuclear translocation of phosphatidylinositol 3-kinase gamma. A Gbetagamma-dependent pathway that requires the p110gamma amino terminus. J Biol Chem 274:27943–27947

    PubMed  CAS  Google Scholar 

  • Musselman CA, Kutateladze TG (2009) PHD fingers: epigenetic effectors and potential drug targets. Mol Interv 9:314–323

    PubMed  CAS  Google Scholar 

  • Ndamukong I, Jones DR, Lapko H, Divecha N, Avramova Z (2010) Phosphatidylinositol 5-phosphate links dehydration stress to the activity of ARABIDOPSIS TRITHORAX-LIKE factor ATX1. PLoS One 5:e13396

    PubMed  Google Scholar 

  • Nelson TJ, Sun MK, Hongpaisan J, Alkon DL (2008) Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair. Eur J Pharmacol 585:76–87

    PubMed  CAS  Google Scholar 

  • Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308:693–698

    PubMed  CAS  Google Scholar 

  • O’Carroll SJ, Mitchell MD, Faenza I, Cocco L, Gilmour RS (2009) Nuclear PLCbeta1 is required for 3T3-L1 adipocyte differentiation and regulates expression of the cyclin D3-cdk4 complex. Cell Signal 21:926–935

    PubMed  Google Scholar 

  • Odom AR, Stahlberg A, Wente SR, York JD (2000) A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 287:2026–2029

    PubMed  CAS  Google Scholar 

  • Osborne SL, Thomas CL, Gschmeissner S, Schiavo G (2001) Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J Cell Sci 114:2501–2511

    PubMed  CAS  Google Scholar 

  • Payrastre B, Nievers M, Boonstra J, Breton M, Verkleij AJ, Van Bergen En Henegouwen PM (1992) A differential location of phosphoinositide kinases, diacylglycerol kinase, and phospholipase C in the nuclear matrix. J Biol Chem 267:5078–5084

    PubMed  CAS  Google Scholar 

  • Peruzzi D, Calabrese G, Faenza I, Manzoli L, Matteucci A, Gianfrancesco F, Billi AM, Stuppia L, Palka G, Cocco L (2000) Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(1). Biochim Biophys Acta 1484:175–182

    PubMed  CAS  Google Scholar 

  • Piazzi M, Bavelloni A, Faenza I, Blalock W, Urbani A, D’Aguanno S, Fiume R, Ramazzotti G, Maraldi NM, Cocco L (2010) eEF1A phosphorylation in the nucleus of insulin-stimulated C2C12 myoblasts: Ser(3) is a novel substrate for protein kinase C betaI. Mol Cell Proteomics 9:2719–2728

    PubMed  CAS  Google Scholar 

  • Pien S, Fleury D, Mylne JS, Crevillen P, Inze D, Avramova Z, Dean C, Grossniklaus U (2008) ARABIDOPSIS TRITHORAX1 dynamically regulates FLOWERING LOCUS C activation via histone 3 lysine 4 trimethylation. Plant Cell 20:580–588

    PubMed  CAS  Google Scholar 

  • Raj K, John A, Ho A, Chronis C, Khan S, Samuel J, Pomplun S, Thomas NS, Mufti GJ (2007) CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. Leukemia 21:1937–1944

    PubMed  CAS  Google Scholar 

  • Ramazzotti G, Faenza I, Gaboardi GC, Piazzi M, Bavelloni A, Fiume R, Manzoli L, Martelli AM, Cocco L (2008) Catalytic activity of nuclear PLC-beta(1) is required for its signalling function during C2C12 differentiation. Cell Signal 20:2013–221

    Google Scholar 

  • Rando OJ, Zhao K, Janmey P, Crabtree GR (2002) Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci U S A 99:2824–2829

    PubMed  CAS  Google Scholar 

  • Resnick AC, Saiardi A (2008) Inositol polyphosphate multikinase: metabolic architect of nuclear inositides. Front Biosci 13:856–866

    PubMed  CAS  Google Scholar 

  • Resnick AC, Snowman AM, Kang BN, Hurt KJ, Snyder SH, Saiardi A (2005) Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity. Proc Natl Acad Sci U S A 102:12783–12788

    PubMed  CAS  Google Scholar 

  • Rodrigues MA, Gomes DA, Leite MF, Grant W, Zhang L, Lam W, Cheng YC, Bennett AM, Nathanson MH (2007) Nucleoplasmic calcium is required for cell proliferation. J Biol Chem 282:17061–17068

    PubMed  CAS  Google Scholar 

  • Rodrigues MA, Gomes DA, Andrade VA, Leite MF, Nathanson MH (2008) Insulin induces calcium signals in the nucleus of rat hepatocytes. Hepatology 48:1621–1631

    PubMed  CAS  Google Scholar 

  • Rodrigues MA, Gomes DA, Nathanson MH, Leite MF (2009) Nuclear calcium signaling: a cell within a cell. Braz J Med Biol Res 42:17–20

    PubMed  CAS  Google Scholar 

  • Ruthenburg AJ, Li H, Patel DJ, Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8:983–994

    PubMed  CAS  Google Scholar 

  • Schill NJ, Anderson RA (2009) Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. Biochem J 422:473–482

    PubMed  CAS  Google Scholar 

  • Scott BL, Deeg HJ (2010) Myelodysplastic syndromes. Annu Rev Med 61:345–358

    PubMed  CAS  Google Scholar 

  • Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Pena P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Cote J, Chua KF, Gozani O (2006) ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442:96–99

    PubMed  CAS  Google Scholar 

  • Sindic A, Crljen V, Matkovic K, Lukinovic-SKUDAR V, Visnjic D, Banfic H (2006) Activation of phosphoinositide 3-kinase C2 beta in the nuclear matrix during compensatory liver growth. Adv Enzyme Regul 46:280–287

    PubMed  CAS  Google Scholar 

  • Smith CD, Wells WW (1983a) Phosphorylation of rat liver nuclear envelopes. I. Characterization of in vitro protein phosphorylation. J Biol Chem 258:9360–9367

    CAS  Google Scholar 

  • Smith CD, Wells WW (1983b) Phosphorylation of rat liver nuclear envelopes. II. Characterization of in vitro lipid phosphorylation. J Biol Chem 258:9368–9373

    CAS  Google Scholar 

  • Smith CD, Wells WW (1984a) Characterization of a phosphatidylinositol 4-phosphate-specific phosphomonoesterase in rat liver nuclear envelopes. Arch Biochem Biophys 235:529–537

    CAS  Google Scholar 

  • Smith CD, Wells WW (1984b) Solubilization and reconstitution of a nuclear envelope-associated ATPase. Synergistic activation by RNA and polyphosphoinositides. J Biol Chem 259:11890–11894

    CAS  Google Scholar 

  • Stallings JD, Tall EG, Pentyala S, Rebecchi MJ (2005) Nuclear translocation of phospholipase C-delta1 is linked to the cell cycle and nuclear phosphatidylinositol 4,5-bisphosphate. J Biol Chem 280:22060–22069

    PubMed  CAS  Google Scholar 

  • Stallings JD, Zeng YX, Narvaez F, Rebecchi MJ (2008) Phospholipase C-delta1 expression is linked to proliferation, DNA synthesis, and cyclin E levels. J Biol Chem 283:13992–14001

    PubMed  CAS  Google Scholar 

  • Sun B, Murray NR, Fields AP (1997) A role for nuclear phosphatidylinositol-specific phospholipase C in the G2/M phase transition. J Biol Chem 272:26313–26317

    PubMed  CAS  Google Scholar 

  • Sylvia V, Curtin G, Norman J, Stec J, Busbee D (1988) Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate. Cell 54:651–658

    PubMed  CAS  Google Scholar 

  • Sylvia VL, Joe CO, Norman JO, Curtin GM, Tilley RD, Busbee DL (1989) Interaction of phosphatidylinositol-4-monophosphate with a low activity form of DNA polymerase alpha: a potential mechanism for enzyme activation. Int J Biochem 21:347–353

    PubMed  CAS  Google Scholar 

  • Tsui MM, York JD (2010) Roles of inositol phosphates and inositol pyrophosphates in development, cell signaling and nuclear processes. Adv Enzyme Regul 50:324–337

    PubMed  Google Scholar 

  • Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M, Majerus PW (2005) The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases. Proc Natl Acad Sci U S A 102:18854–18859

    PubMed  CAS  Google Scholar 

  • van den Bout I, Divecha N (2009) PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions. J Cell Sci 122:3837–3850

    PubMed  Google Scholar 

  • Vandromme M, Rochat A, Meier R, Carnac G, Besser D, Hemmings BA, Fernandez A, Lamb NJ (2001) Protein kinase B beta/Akt2 plays a specific role in muscle differentiation. J Biol Chem 276:8173–8179

    PubMed  CAS  Google Scholar 

  • Vann LR, Wooding FB, Irvine RF, Divecha N (1997) Metabolism and possible compartmentalization of inositol lipids in isolated rat-liver nuclei. Biochem J 327(Pt 2):569–576

    PubMed  CAS  Google Scholar 

  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le BEAU MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951

    PubMed  CAS  Google Scholar 

  • Vermeulen M, Mulder KW, Denissov S, Pijnappel WW, Van Schaik FM, Varier RA, Baltissen MP, Stunnenberg HG, Mann M, Timmers HT (2007) Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131:58–69

    PubMed  CAS  Google Scholar 

  • Visnjic D, Banfic H (2007) Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase. Pflugers Arch 455:19–30

    PubMed  CAS  Google Scholar 

  • Visnjic D, Crljen V, Curic J, Batinic D, Volinia S, Banfic H (2002) The activation of nuclear phosphoinositide 3-kinase C2beta in all-trans-retinoic acid-differentiated HL-60 cells. FEBS Lett 529:268–274

    PubMed  CAS  Google Scholar 

  • Visnjic D, Curic J, Crljen V, Batinic D, Volinia S, Banfic H (2003) Nuclear phosphoinositide 3-kinase C2beta activation during G2/M phase of the cell cycle in HL-60 cells. Biochim Biophys Acta 1631:61–71

    PubMed  CAS  Google Scholar 

  • Walker SD, Murray NR, Burns DJ, Fields AP (1995) Protein kinase C chimeras: catalytic domains of alpha and beta II protein kinase C contain determinants for isotype-specific function. Proc Natl Acad Sci U S A 92:9156–9160

    PubMed  CAS  Google Scholar 

  • Walker DM, Urbe S, Dove SK, Tenza D, Raposo G, Clague MJ (2001) Characterization of MTMR3. An inositol lipid 3-phosphatase with novel substrate specificity. Curr Biol 11:1600–1605

    PubMed  CAS  Google Scholar 

  • Wang M, Bond NJ, Letcher AJ, Richardson JP, Lilley KS, Irvine RF, Clarke JH (2010) Genomic tagging reveals a random association of endogenous PtdIns5P 4-kinases IIalpha and IIbeta and a partial nuclear localization of the IIalpha isoform. Biochem J 430:215–221

    Google Scholar 

  • Watt SA, Kular G, Fleming IN, Downes CP, Lucocq JM (2002) Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C delta1. Biochem J 363:657–666

    PubMed  CAS  Google Scholar 

  • Wysocka J, Swigut T, Xiao H, Milne TA, Kwon SY, Landry J, Kauer M, Tackett AJ, Chait BT, Badenhorst P, Wu C, Allis CD (2006) A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442:86–90

    PubMed  CAS  Google Scholar 

  • Xia X, Cheng A, Akinmade D, Hamburger AW (2003) The N-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest. Mol Cell Biol 23:1717–1725

    PubMed  CAS  Google Scholar 

  • Xu A, Suh PG, Marmy-Conus N, Pearson RB, Seok OY, Cocco L, Gilmour RS (2001) Phosphorylation of nuclear phospholipase C beta1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I. Mol Cell Biol 21:2981–2990

    PubMed  CAS  Google Scholar 

  • Ye K (2005) PIKE/nuclear PI 3-kinase signaling in preventing programmed cell death. J Cell Biochem 96:463–472

    PubMed  CAS  Google Scholar 

  • York JD, Majerus PW (1994) Nuclear phosphatidylinositols decrease during S-phase of the cell cycle in HeLa cells. J Biol Chem 269:7847–7850

    PubMed  CAS  Google Scholar 

  • York JD, Odom AR, Murphy R, Ives EB, Wente SR (1999) A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 285:96–100

    PubMed  CAS  Google Scholar 

  • Yu H, Fukami K, Watanabe Y, Ozaki C, Takenawa T (1998) Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. Eur J Biochem 251:281–287

    PubMed  CAS  Google Scholar 

  • Zeng L, Zhang Q, Li S, Plotnikov AN, Walsh MJ, Zhou MM (2010) Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature 466:258–262

    PubMed  CAS  Google Scholar 

  • Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR (1998) Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95:625–636

    PubMed  CAS  Google Scholar 

  • Zou J, Marjanovic J, Kisseleva MV, Wilson M, Majerus PW (2007) Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis. Proc Natl Acad Sci U S A 104:16834–16839

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by funding from the Italian MIUR-FIRB Human Proteome Net, Italian CARISBO Foundation, and Celgene Corp. Work in the laboratory of N. Divecha was funded by the Dutch Cancer Society and by CRUK.

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  1. Cellular Signalling Laboratory, Department of Human Anatomical Sciences, University of Bologna, Bologna, Italy

    Roberta Fiume & Lucio Cocco

  2. CRUK Inositide Laboratory, The Paterson Institute for Cancer Research, M204BX, Manchester, United Kingdom

    Nullin Divecha

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  1. Roberta Fiume
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  2. Willem Jan Keune
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Correspondence to Roberta Fiume .

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  1. , NICHD, National Institutes of Health, Convent Drive 49, Bethesda, 20892-4480, Maryland, USA

    Tamas Balla

  2. , Cancer- and Immunobiology, University of Basel, Mattenstrasse 28, Basel, 4058, Switzerland

    Matthias Wymann

  3. , Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    John D. York

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Fiume, R. et al. (2012). Nuclear Phosphoinositides: Location, Regulation and Function. In: Balla, T., Wymann, M., York, J. (eds) Phosphoinositides II: The Diverse Biological Functions. Subcellular Biochemistry, vol 59. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3015-1_11

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