Skip to main content
SpringerLink
Log in

Shared genes in rheumatic diseases, the role of PD1 and the RUNX genes in disease susceptibility

  • Chapter
Book cover The Hereditary Basis of Rheumatic Diseases

Part of the book series: Progress in Inflammation Research ((PIR))

  • 541 Accesses

Concluding remarks

In this chapter we have reviewed the role of PDCD1 and the RUNX family of genes in the pathogenesis of rheumatic diseases. Much still needs to be done in order to understand how the pathophysiology involving these genes leads to the development of these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alarcón-Segovia D, Alarcón-Riquelme ME, Cardiel MH, Caeiro F, Massardo L, Villa AR, Pons-Estel BA; Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL) (2005) Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis Rheum 52: 1138–1147

    Article  PubMed  Google Scholar 

  2. Ishida Y, Agata Y, Shibahara K, Honjo T (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. Embo J 11: 3887–3895

    PubMed  CAS  Google Scholar 

  3. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T (1996) Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol 8: 765–772

    PubMed  CAS  Google Scholar 

  4. Nishimura H, Minato N, Nakano T, Honjo T (1998) Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol 10: 1563–1572

    Article  PubMed  CAS  Google Scholar 

  5. Nishimura H, Nose M, Hiai H, Minato N, Honjo T (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11: 141–151

    Article  PubMed  CAS  Google Scholar 

  6. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T (2001) Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291: 319–322

    Article  PubMed  CAS  Google Scholar 

  7. Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T (1994) Structure and chromosomal localization of the human PD-1 gene (PDCD1). Genomics 23: 704–706

    Article  PubMed  CAS  Google Scholar 

  8. Lindqvist AK, Steinsson K, Johanneson B, Kristjansdottir H, Arnasson A, Grondal G, Jonasson I, Magnusson V, Sturfelt G, Truedsson L et al (2000) A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun 14:169–178

    Article  PubMed  CAS  Google Scholar 

  9. Magnusson V, Lindqvist AK, Castillejo-Lopez C, Kristjansdottir H, Steinsson K, Grondal G, Sturfelt G, Truedsson L, Svenungsson E, Lundberg I et al (2000) Fine mapping of the SLEB2 locus involved in susceptibility to systemic lupus erythematosus. Genomics 70: 307–314

    Article  PubMed  CAS  Google Scholar 

  10. Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G et al (2002) A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 32: 666–669

    Article  PubMed  CAS  Google Scholar 

  11. Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST (2003) Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens 62: 492–497

    Article  PubMed  CAS  Google Scholar 

  12. Nielsen C, Laustrup H, Voss A, Junker P, Husby S, Lillevang ST (2004) A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients. Lupus 13: 510–516

    Article  PubMed  CAS  Google Scholar 

  13. Prokunina L, Padyukov L, Bennet A, de Faire U, Wiman B, Prince J, Alfredsson L, Klareskog L, Alarcon-Riquelme M (2004) Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum 50: 1770–1773

    Article  PubMed  CAS  Google Scholar 

  14. Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW, Chen CJ (2004) Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum 50: 770–775

    Article  PubMed  CAS  Google Scholar 

  15. Kong EK, Prokunina-Olsson L, Wong WH, Lau CS, Chan TM, Alarcon-Riquelme M, Lau YL (2005) A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese. Arthritis Rheum 52: 1058–1062

    Article  PubMed  CAS  Google Scholar 

  16. Berardi MJ, Sun C, Zehr M, Abildgaard F, Peng J, Speck NA, Bushweller JH (1999) The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure Fold Des 7:1247–1256

    Article  PubMed  CAS  Google Scholar 

  17. Zhang YW, Bae SC, Takahashi E, Ito Y (1997) The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia. Oncogene 15: 367–371

    Article  PubMed  CAS  Google Scholar 

  18. Zent C, Kim N, Hiebert S, Zhang DE, Tenen DG, Rowley JD, Nucifora G (1996) Rearrangement of the AML1/CBFA2 gene in myeloid leukemia with the 3;21 translocation: expression of co-existing multiple chimeric genes with similar functions as transcriptional repressors, but with opposite tumorigenic properties. Curr Top Microbiol Immunol 211: 243–252

    PubMed  CAS  Google Scholar 

  19. Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben-Asher E, Lancet D, Levanon D, Groner Y (2001) The RUNX3 gene—sequence, structure and regulated expression. Gene 279: 221–232

    Article  PubMed  CAS  Google Scholar 

  20. Lindqvist AK, Alarcon-Riquelme ME (1999) The genetics of systemic lupus erythematosus. Scand J Immunol 50: 562–571

    Article  PubMed  CAS  Google Scholar 

  21. Levanon D, Groner Y (2004) Structure and regulated expression of mammalian RUNX genes. Oncogene 23: 4211–4219

    Article  PubMed  CAS  Google Scholar 

  22. Ito Y (1999) Molecular basis of tissue-specific gene expression mediated by the runt domain transcription factor PEBP2/CBF. Genes Cells 4: 685–696

    Article  PubMed  CAS  Google Scholar 

  23. Stein GS, van Wijnen AJ, Stein JL, Lian JB, Pockwinse S, McNeil S (1998) Interrelationships of nuclear structure and transcriptional control: functional consequences of being in the right place at the right time. J Cell Biochem 70: 200–212

    Article  PubMed  CAS  Google Scholar 

  24. Stewart M, Terry A, Hu M, O’Hara M, Blyth K, Baxter E, Cameron E, Onions DE, Neil JC (1997) Proviral insertions induce the expression of bone-specific isoforms of PEBP2alphaA (CBFA1): evidence for a new myc collaborating oncogene. Proc Natl Acad Sci USA 94: 8646–8651

    Article  PubMed  CAS  Google Scholar 

  25. Xiao ZS, Thomas R, Hinson TK, Quarles LD (1998) Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor. Gene 214:187–197

    Article  PubMed  CAS  Google Scholar 

  26. Xiao ZS, Liu SG, Hinson TK, Quarles LD (2001) Characterization of the upstream mouse Cbfa1/Runx2 promoter. J Cell Biochem 82: 647–659

    Article  PubMed  CAS  Google Scholar 

  27. Tsuji K, Noda M (2000) Identification and expression of a novel 3′-exon of mouse Runx1/Pebp2alphaB/Cbfa2/AML1 gene. Biochem Biophys Res Commun 274: 171–176

    Article  PubMed  CAS  Google Scholar 

  28. Stein GS, Lian JB, Stein JL, van Wijnen AJ, Montecino M, Pratap J, Choi J, Zaidi SK, Javed A, Gutierrez S, Harrington K, Shen J, Young D (2003) Intranuclear organization of RUNX transcriptional regulatory machinery in biological control of skeletogenesis and cancer. Blood Cells Mol Dis 30: 170–176

    Article  PubMed  CAS  Google Scholar 

  29. Rini D, Calabi F (2001) Identification and comparative analysis of a second runx3 promoter. Gene 273: 13–22

    Article  PubMed  CAS  Google Scholar 

  30. Backstrom S, Huang SH, Wolf-Watz M, Xie XQ, Hard T, Grundstrom T, Sauer UH (2001) Crystallization and preliminary studies of the DNA-binding runt domain of AML1. Acta Crystallogr D Biol Crystallogr 57: 269–271

    Article  PubMed  CAS  Google Scholar 

  31. Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y (2001) Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. Embo J 20: 723–733

    Article  PubMed  CAS  Google Scholar 

  32. Tahirov TH, Inoue-Bungo T, Morii H, Fujikawa A, Sasaki M, Kimura K, Shiina M, Sato K, Kumasaka T, Yamamoto M, Ishii S, Ogata K (2001) Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Cell 104: 755–767

    Article  PubMed  CAS  Google Scholar 

  33. Tahirov TH, Inoue-Bungo T, Sasaki M, Shiina M, Kimura K, Sato K, Kumasaka T, Yamamoto M, Kamiya N, Ogata K (2001) Crystallization and preliminary X-ray analyses of quaternary, ternary and binary protein-DNA complexes with involvement of AML1/Runx-1/CBFalpha Runt domain, CBFbeta and the C/EBPbeta bZip region. Acta Crystallogr D Biol Crystallogr 57: 850–853

    Article  PubMed  CAS  Google Scholar 

  34. Zent C, Rowley JD, Nucifora G (1997) Rearrangements of the AML1/CBFA2 gene in myeloid leukemia with the 3;21 translocation: in vitro and in vivo studies. Leukemia 11(Suppl 3): 273–278

    PubMed  Google Scholar 

  35. Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW (2000) A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. J Biol Chem 275: 651–656

    Article  PubMed  CAS  Google Scholar 

  36. Lo Coco F, Pisegna S, Diverio D (1997) The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias. Haematologica 82: 364–370

    PubMed  Google Scholar 

  37. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89: 755–764

    Article  PubMed  CAS  Google Scholar 

  38. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89: 747–754

    Article  PubMed  CAS  Google Scholar 

  39. Stricker S, Fundele R, Vortkamp A, Mundlos S (2002) Role of Runx genes in chondrocyte differentiation. Dev Biol 245: 95–108

    Article  PubMed  CAS  Google Scholar 

  40. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH et al (1997) Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89: 773–779

    Article  PubMed  CAS  Google Scholar 

  41. Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB et al (2002) Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 109: 113–124

    Article  PubMed  CAS  Google Scholar 

  42. Li QL, Kim HR, Kim WJ, Choi JK, Lee YH, Kim HM, Li LS, Kim H, Chang J, Ito Y et al (2004) Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer. Biochem Biophys Res Commun 314: 223–228

    Article  PubMed  CAS  Google Scholar 

  43. Kundu M, Liu PP (2003) Cbf beta is involved in maturation of all lineages of hematopoietic cells during embryogenesis except erythroid. Blood Cells Mol Dis 30:164–169

    Article  PubMed  CAS  Google Scholar 

  44. Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y, Littman DR (2002) Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111: 621–633

    Article  PubMed  CAS  Google Scholar 

  45. Taniuchi I, Littman DR (2004) Epigenetic gene silencing by Runx proteins. Oncogene 23: 4341–4345

    Article  PubMed  CAS  Google Scholar 

  46. Vaillant F, Blyth K, Andrew L, Neil JC, Cameron ER (2002) Enforced expression of Runx2 perturbs T cell development at a stage coincident with beta-selection. J Immunol 169: 2866–2874

    PubMed  CAS  Google Scholar 

  47. Drissi H, Luc Q, Shakoori R, Chuva De Sousa Lopes S, Choi JY, Terry A, Hu M, Jones S, Neil JC, Lian JB et al (2000) Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene. J Cell Physiol 184: 341–350

    Article  PubMed  CAS  Google Scholar 

  48. Spender LC, Whiteman HJ, Karstegl CE, Farrell PJ (2005) Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells. Oncogene 24: 1873–1881

    Article  PubMed  CAS  Google Scholar 

  49. Sakakura C, Hagiwara A, Miyagawa K, Nakashima S, Yoshikawa T, Kin S, Nakase Y, Ito K, Yamagishi H, Yazumi S et al (2005) Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer. Int J Cancer 113: 221–228

    Article  PubMed  CAS  Google Scholar 

  50. Lee KS, Kim HJ, Li QL, Chi XZ, Ueta C, Komori T, Wozney JM, Kim EG, Choi JY, Ryoo HM, Bae SC (2000) Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol 20: 8783–8792

    Article  PubMed  CAS  Google Scholar 

  51. Leboy P, Grasso-Knight G, D’Angelo M, Volk SW, Lian JV, Drissi H, Stein GS, Adams SL (2001) Smad-Runx interactions during chondrocyte maturation. J Bone Joint Surg Am 83-A(Suppl 1): S15–S22

    PubMed  Google Scholar 

  52. Ito Y, Miyazono K (2003) RUNX transcription factors as key targets of TGF-beta superfamily signaling. Curr Opin Genet Dev 13: 43–47

    Article  PubMed  CAS  Google Scholar 

  53. Tou L, Quibria N, Alexander JM (2003) Transcriptional regulation of the human Runx2/Cbfa1 gene promoter by bone morphogenetic protein-7. Mol Cell Endocrinol 205: 121–129

    Article  PubMed  CAS  Google Scholar 

  54. Selvamurugan N, Kwok S, Partridge NC (2004) Smad3 interacts with JunB and Cbfa1/Runx2 for transforming growth factor-beta1-stimulated collagenase-3 expression in human breast cancer cells. J Biol Chem 279: 27764–27773

    Article  PubMed  CAS  Google Scholar 

  55. Ji C, Eickelberg O, McCarthy TL, Centrella M (2001) Control and counter-control of TGF-beta activity through FAST and Runx (CBFa) transcriptional elements in osteoblasts. Endocrinology 142: 3873–3879

    Article  PubMed  CAS  Google Scholar 

  56. Shi MJ, Park SR, Kim PH, Stavnezer J (2001) Roles of Ets proteins, NF-kappa B and nocodazole in regulating induction of transcription of mouse germline Ig alpha RNA by transforming growth factor-beta 1. Int Immunol 13: 733–767

    Article  PubMed  CAS  Google Scholar 

  57. Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D, Negreanu V, Bernstein Y, Levanon D, Jung S, Groner Y (2004) Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. Embo J 23:969–979

    Article  PubMed  CAS  Google Scholar 

  58. Brenner O, Levanon D, Negreanu V, Golubkov O, Fainaru O, Woolf E, Groner Y (2004) Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia. Proc Natl Acad Sci USA 101: 16016–16021

    Article  PubMed  CAS  Google Scholar 

  59. Komine O, Hayashi K, Natsume W, Watanabe T, Seki Y, Seki N, Yagi R, Sukzuki W, Tamauchi H, Hozumi K et al (2003) The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression. J Exp Med 198: 51–61

    Article  PubMed  CAS  Google Scholar 

  60. Suwa A, Hirakata M, Satoh S, Ezaki T, Mimori T, Inada S (2000) Systemic lupus erythematosus associated with Down syndrome. Clin Exp Rheumatol 18: 650–651

    PubMed  CAS  Google Scholar 

  61. Feingold M, Schneller S (1995) Down syndrome and systemic lupus erythematosus. Clin Genet 48: 277

    Article  PubMed  CAS  Google Scholar 

  62. Osato M (2004) Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia. Oncogene 23: 4284–4296

    Article  PubMed  CAS  Google Scholar 

  63. Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R et al (1999) Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 23: 166–175

    Article  PubMed  CAS  Google Scholar 

  64. Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M et al (2003) An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet 35: 341–348. Epub 2003 Nov 9

    Article  PubMed  CAS  Google Scholar 

  65. Helms C, Cao L, Krueger JG, Wijsman EM, Chamian F, Gordon D, Heffernan M, Daw JA, Robarge J, Ott J et al (2003) A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Nat Genet 35:349–56. Epub 2003 Nov 9

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden

    Marta E. Alarcón-Riquelme & Sergey V. Kozyrev

Authors
  1. Marta E. Alarcón-Riquelme
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergey V. Kozyrev
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Section for Medical Inflammation Research, Department of Cell and Molecular Biology, Lund University, Solvegatan 19, I11 BMC, S-221 84, Lund, Sweden

    Rikard Holmdahl

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Alarcón-Riquelme, M.E., Kozyrev, S.V. (2006). Shared genes in rheumatic diseases, the role of PD1 and the RUNX genes in disease susceptibility. In: Holmdahl, R. (eds) The Hereditary Basis of Rheumatic Diseases. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7419-5_6

Download citation

  • DOI: https://doi.org/10.1007/3-7643-7419-5_6

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-7201-9

  • Online ISBN: 978-3-7643-7419-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation