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The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey

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Abstract

The expression of the murine p200 family protein p204 in numerous tissues can be activated by a variety of distinct, tissue-specific transcription factors. p204 modulates cell proliferation, cell cycling, and the differentiation of various tissues, including skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes, and macrophages. This protein modulates these processes in various ways, such as by (1) blocking ribosomal RNA synthesis in the nucleolus, (2) inhibiting Ras signaling in the cytoplasm, (3) promoting the activity of particular transcription factors in the nucleus by forming complexes with them, and (4) overcoming the block of the activity of other transcription factors by inhibitor of differentiation (Id) proteins. Much remains to be learned about p204, particularly with respect to its expected involvement in the differentiation of several as yet unexplored tissues.

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References

  1. Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, Stark GR (2007) Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov 6:975–990

    Article  CAS  PubMed  Google Scholar 

  2. Fensterl V, Sen GC (2009) Interferons and viral infections. Biofactors 35:14–20

    Article  CAS  PubMed  Google Scholar 

  3. Farrell PJ, Broeze RJ, Lengyel P (1979) Accumulation of an mRNA and protein in interferon-treated Ehrlich ascites tumour cells. Nature 279:523–525

    Article  CAS  PubMed  Google Scholar 

  4. Lengyel P (2008) From RNase L to the multitalented p200 family proteins: an exploration of the modes of interferon action. J Interferon Cytokine Res 28:273–281

    Article  CAS  PubMed  Google Scholar 

  5. Samanta H, Dougherty JP, Brawner ME, Schmidt H, Lengyel P (1982) Interferon action: cloning of cDNA segments complementary to messenger RNAs induced by interferons. In: Merigan T, Friedman R, Fox CF (eds) Chemistry and biology of interferons relationship to therapeutics: UCLA symposium of molecular and cellular biology. Academic Press, New York, pp 59–72

  6. Choubey D, Snoddy J, Chaturvedi V, Toniato E, Opdenakker G, Thakur A, Samanta H, Engel DA, Lengyel P (1989) Interferons as gene activators. Indications for repeated gene duplication during the evolution of a cluster of interferon-activatable genes on murine chromosome 1. J Biol Chem 264:17182–17189

    CAS  PubMed  Google Scholar 

  7. Deschamps S, Meyer J, Chatterjee G, Wang H, Lengyel P, Roe BA (2003) The mouse Ifi200 gene cluster: genomic sequence, analysis, and comparison with the human HIN-200 gene cluster. Genomics 82:34–46

    Article  CAS  PubMed  Google Scholar 

  8. Opdenakker G, Snoddy J, Choubey D, Toniato E, Pravtcheva DD, Seldin MF, Ruddle FH, Lengyel P (1989) Interferons as gene activators: a cluster of six interferon-activatable genes is linked to the erythroid alpha-spectrin locus on murine chromosome 1. Virology 171:568–578

    Article  CAS  PubMed  Google Scholar 

  9. Ludlow LE, Johnstone RW, Clarke CJ (2005) The HIN-200 family: more than interferon-inducible genes? Exp Cell Res 308:1–17

    Article  CAS  PubMed  Google Scholar 

  10. Asefa B, Klarmann KD, Copeland NG, Gilbert DJ, Jenkins NA, Keller JR (2004) The interferon-inducible p200 family of proteins: a perspective on their roles in cell cycle regulation and differentiation. Blood Cells Mol Dis 32:155–167

    Article  CAS  PubMed  Google Scholar 

  11. Johnstone RW, Kershaw MH, Trapani JA (1998) Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing. Biochemistry 37:11924–11931

    Article  CAS  PubMed  Google Scholar 

  12. DeYoung KL, Ray ME, Su YA, Anzick SL, Johnstone RW, Trapani JA, Meltzer PS, Trent JM (1997) Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. Oncogene 15:453–457

    Article  CAS  PubMed  Google Scholar 

  13. Wang H, Chatterjee G, Meyer JJ, Liu CJ, Manjunath NA, Bray-Ward P, Lengyel P (1999) Characteristics of three homologous 202 genes (Ifi202a, Ifi202b, and Ifi202c) from the murine interferon-activatable gene 200 cluster. Genomics 60:281–294

    Article  CAS  PubMed  Google Scholar 

  14. Ding Y, Lee JF, Lu H, Lee MH, Yan DH (2006) Interferon-inducible protein IFIXalpha1 functions as a negative regulator of HDM2. Mol Cell Biol 26:1979–1996

    Article  CAS  PubMed  Google Scholar 

  15. Zhang Y, Tian Q, Du Y, Cao H, Lengyel P, Kong W (2008) Multiple splicing results in at least two p203 proteins that are expressed in the liver and down-regulated during liver regeneration. Front Biosci 13:2444–2451

    Article  CAS  PubMed  Google Scholar 

  16. Choubey D, Panchanathan R (2008) Interferon-inducible Ifi200-family genes in systemic lupus erythematosus. Immunol Lett 119:32–41

    Article  CAS  PubMed  Google Scholar 

  17. Ding B, Lengyel P (2008) p204 protein is a novel modulator of Ras activity. J Biol Chem 283:5831–5848

    Article  CAS  PubMed  Google Scholar 

  18. Wang H, Liu C, Lu Y, Chatterjee G, Ma XY, Eisenman RN, Lengyel P (2000) The interferon- and differentiation-inducible p202a protein inhibits the transcriptional activity of c-Myc by blocking its association with Max. J Biol Chem 275:27377–27385

    CAS  PubMed  Google Scholar 

  19. Min W, Ghosh S, Lengyel P (1996) The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. Mol Cell Biol 16:359–368

    CAS  PubMed  Google Scholar 

  20. Liu CJ, Wang H, Lengyel P (1999) The interferon-inducible nucleolar p204 protein binds the ribosomal RNA-specific UBF1 transcription factor and inhibits ribosomal RNA transcription. EMBO J 18:2845–2854

    Article  CAS  PubMed  Google Scholar 

  21. Luan Y, Lengyel P, Liu CJ (2008) p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation. Cytokine Growth Factor Rev 19:357–369

    Article  CAS  PubMed  Google Scholar 

  22. Lengyel P, Choubey D, Li S-J, Datta B (1995) The interferon-activatable gene 200 cluster: from structure toward function. Semin Virol 6:203–213

    Article  CAS  Google Scholar 

  23. Lembo M, Sacchi C, Zappador C, Bellomo G, Gaboli M, Pandolfi PP, Gariglio M, Landolfo S (1998) Inhibition of cell proliferation by the interferon-inducible 204 gene, a member of the Ifi 200 cluster. Oncogene 16:1543–1551

    Article  CAS  PubMed  Google Scholar 

  24. Choubey D, Lengyel P (1992) Interferon action: nucleolar and nucleoplasmic localization of the interferon-inducible 72-kD protein that is encoded by the Ifi 204 gene from the gene 200 cluster. J Cell Biol 116:1333–1341

    Article  CAS  PubMed  Google Scholar 

  25. Liu C, Wang H, Zhao Z, Yu S, Lu YB, Meyer J, Chatterjee G, Deschamps S, Roe BA, Lengyel P (2000) MyoD-dependent induction during myoblast differentiation of p204, a protein also inducible by interferon. Mol Cell Biol 20:7024–7036

    Article  CAS  PubMed  Google Scholar 

  26. Liu CJ, Ding B, Wang H, Lengyel P (2002) The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins. Mol Cell Biol 22:2893–2905

    Article  CAS  PubMed  Google Scholar 

  27. Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990) The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61:49–59

    Article  CAS  PubMed  Google Scholar 

  28. Iavarone A, Garg P, Lasorella A, Hsu J, Israel MA (1994) The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein. Genes Dev 8:1270–1284

    Article  CAS  PubMed  Google Scholar 

  29. Norton JD, Deed RW, Craggs G, Sablitzky F (1998) Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol 8:58–65

    Article  CAS  PubMed  Google Scholar 

  30. Ding B, Liu CJ, Huang Y, Yu J, Kong W, Lengyel P (2006) p204 protein overcomes the inhibition of the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes by Id proteins. J Biol Chem 281:14893–14906

    Article  CAS  PubMed  Google Scholar 

  31. Ding B, Liu CJ, Huang Y, Hickey RP, Yu J, Kong W, Lengyel P (2006) p204 is required for the differentiation of p19 murine embryonal carcinoma cells to beating cardiac myocytes: its expression is activated by the cardiac Gata4, Nkx2.5, and Tbx5 proteins. J Biol Chem 281:14882–14892

    Article  CAS  PubMed  Google Scholar 

  32. Liu CJ, Chang E, Yu J, Carlson CS, Prazak L, Yu XP, Ding B, Lengyel P, Di Cesare PE (2005) The interferon-inducible p204 protein acts as a transcriptional coactivator of Cbfa1 and enhances osteoblast differentiation. J Biol Chem 280:2788–2796

    Article  CAS  PubMed  Google Scholar 

  33. Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ (2007) The retinoblastoma protein is an essential mediator of osteogenesis that links the p204 protein to the Cbfa1 transcription factor thereby increasing its activity. J Biol Chem 282:16860–16870

    Article  CAS  PubMed  Google Scholar 

  34. Thomas DM, Carty SA, Piscopo DM, Lee JS, Wang WF, Forrester WC, Hinds PW (2001) The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol Cell 8:303–316

    Article  CAS  PubMed  Google Scholar 

  35. Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127:1755–1766

    Article  CAS  PubMed  Google Scholar 

  36. Ogata T, Wozney JM, Benezra R, Noda M (1993) Bone morphogenetic protein 2 transiently enhances expression of a gene, Id (inhibitor of differentiation), encoding a helix-loop-helix molecule in osteoblast-like cells. Proc Natl Acad Sci USA 90:9219–9222

    Article  CAS  PubMed  Google Scholar 

  37. Vinals F, Reiriz J, Ambrosio S, Bartrons R, Rosa JL, Ventura F (2004) BMP-2 decreases Mash1 stability by increasing Id1 expression. EMBO J 23:3527–3537

    Article  CAS  PubMed  Google Scholar 

  38. Peng Y, Kang Q, Luo Q, Jiang W, Si W, Liu BA, Luu HH, Park JK, Li X, Luo J, Montag AG, Haydon RC, He TC (2004) Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells. J Biol Chem 279:32941–32949

    Article  CAS  PubMed  Google Scholar 

  39. Luan Y, Yu XP, Yang N, Frenkel S, Chen L, Liu CJ (2008) p204 protein overcomes the inhibition of Cbfa1-mediated osteogenic differentiation by Id helix-loop-helix proteins. Mol Biol Cell 19:2113–2126

    Article  CAS  PubMed  Google Scholar 

  40. Karsenty G, Wagner EF (2002) Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2:389–406

    Article  CAS  PubMed  Google Scholar 

  41. Atkinson BL, Fantle KS, Benedict JJ, Huffer WE, Gutierrez-Hartmann A (1997) Combination of osteoinductive bone proteins differentiates mesenchymal C3H/10T1/2 cells specifically to the cartilage lineage. J Cell Biochem 65:325–339

    Article  CAS  PubMed  Google Scholar 

  42. Zhang Y, Kong L, Carlson CS, Liu CJ (2008) Cbfa1-dependent expression of an interferon-inducible p204 protein is required for chondrocyte differentiation. Cell Death Differ 15:1760–1771

    Article  CAS  PubMed  Google Scholar 

  43. Kong L, Liu CJ (2008) Mediation of chondrogenic and osteogenic differentiation by an interferon-inducible p202 protein. Cell Mol Life Sci 65:3494–3506

    Article  CAS  PubMed  Google Scholar 

  44. Dauffy J, Mouchiroud G, Bourette RP (2006) The interferon-inducible gene, Ifi204, is transcriptionally activated in response to M-CSF, and its expression favors macrophage differentiation in myeloid progenitor cells. J Leukocyte Biol 79:173–183

    Article  CAS  PubMed  Google Scholar 

  45. Deftos ML, Huang E, Ojala EW, Forbush KA, Bevan MJ (2000) Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes. Immunity 13:73–84

    Article  CAS  PubMed  Google Scholar 

  46. Malumbres M, Barbacid M (2003) RAS oncogenes: the first 30 years. Nat Rev Cancer 3:459–465

    Article  CAS  PubMed  Google Scholar 

  47. Weinberg RB (2006) The biology of cancer. Garland Science, Oxford

    Google Scholar 

  48. Hertel L, De Andrea M, Azzimonti B, Rolle A, Gariglio M, Landolfo S (1999) The interferon-inducible 204 gene, a member of the Ifi 200 family, is not involved in the antiviral state induction by IFN-alpha, but is required by the mouse cytomegalovirus for its replication. Virology 262:1–8

    Article  CAS  PubMed  Google Scholar 

  49. Rolle S, De Andrea M, Gioia D, Lembo D, Hertel L, Landolfo S, Gariglio M (2001) The interferon-inducible 204 gene is transcriptionally activated by mouse cytomegalovirus and is required for its replication. Virology 286:249–255

    Article  CAS  PubMed  Google Scholar 

  50. Gariglio M, Foresta P, Ying GG, Gaboli M, Lembo D, Landolfo S (1996) Host genotype controls the ability of the ISGF3 complex to activate transcription of IFN-inducible genes. J Cell Biochem 60:83–94

    Article  CAS  PubMed  Google Scholar 

  51. Gariglio M, Panico S, Cavallo G, Divaker C, Lengyel P, Landolfo S (1992) Impaired transcription of the poly rI:rC- and interferon-activatable 202 gene in mice and cell lines from the C57BL/6 strain. Virology 187:115–123

    Article  CAS  PubMed  Google Scholar 

  52. Gariglio M, Gaboli M, Mana C, Ying GG, Gribaudo G, Cavallo R, Landolfo S (1994) Characterization of nuclear factors involved in 202 gene induction by interferon-alpha in murine leukemia cells. Eur J Biochem 221:731–739

    Article  CAS  PubMed  Google Scholar 

  53. Choubey D, Kotzin BL (2002) Interferon-inducible p202 in the susceptibility to systemic lupus. Front Biosci 7:e252–e262

    Article  CAS  PubMed  Google Scholar 

  54. Wang H, Ding B, Liu CJ, Ma XY, Deschamps S, Roe BA, Lengyel P (2002) The increase in levels of interferon-inducible proteins p202a and p202b and RNA-dependent protein kinase (PKR) during myoblast differentiation is due to transactivation by MyoD: their tissue distribution in uninfected mice does not depend on interferons. J Interferon Cytokine Res 22:729–737

    Article  CAS  PubMed  Google Scholar 

  55. Capecchi MR (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6:507–512

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to our gifted collaborators who made the explorations in our laboratories possible. Studies in our laboratories were supported by NIH research grants AI-12320 (to P. L.), and AR050620, AR053210, and AG029388 (to C. J. L.), and a grant from the Arthritis National Research Foundation (to C. J. L.).

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Authors and Affiliations

  1. Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT, 06520-8024, USA

    Peter Lengyel

  2. Department of Orthopaedic Surgery, New York University School of Medicine, 301 East 17th Street, New York, NY, 10003, USA

    C. J. Liu

  3. Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA

    C. J. Liu

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  1. Peter Lengyel
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  2. C. J. Liu
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Correspondence to Peter Lengyel or C. J. Liu.

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Lengyel, P., Liu, C.J. The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey. Cell. Mol. Life Sci. 67, 335–340 (2010). https://doi.org/10.1007/s00018-009-0195-z

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  • DOI: https://doi.org/10.1007/s00018-009-0195-z

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