Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP-1: rheumatoid synovial cells overexpressing these genes go into aberrant mitosis

Oncogene volume 22, pages 6839–6844 (2003)Cite this article

Abstract

Wee1 kinase downregulates the M-phase promoting factor, a complex of cdc2 and cyclin B kinase, that controls mitotic cell division. We isolated human wee1 kinase gene promoter and found that it contained one AP-1-binding motif in its promoter region (5′-CGAGTCA-3′; −823/−817), through which wee1 kinase gene was directly transactivated by c-Fos/AP-1. In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated. The amount of wee1 and c-Fos and the phosphorylation of cdc2 were decreased after treatment of the cells with an inhibitor of AP-1, curcumin. A significant proportion of cultured synovial cells of the patients with rheumatoid arthritis, but not those of osteoarthritis, shifted to a tetraploid (4C) state upon long-term culture. Thus, human wee1 kinase gene is directly transactivated by and increased in association with c-Fos/AP-1, and rheumatoid synovial cells overexpressing these genes go into aberrant mitosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Abbreviations

DIG:

digoxigenin

EMSA:

electrophoretic mobility shift assay

MPF:

M-phase promoting factor

OA:

osteoarthritis

PCNA:

proliferating cell nuclear antigen

PMA:

phorbol 12-myristate 13-acetate

RA:

rheumatoid arthritis

TSS:

transcription start sit

References

  • Aicher WK, Heer AH, Trabandt A, Bridgee Jr SL, Schroeder Jr HW, Stransky G, Gay RE, Eibel H, Peter HH, Siebenlist U, Koopman WJ and Steffen G . (1994). J. Immunol., 152, 5940–5948.

  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger Jr TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL and Hunder GG . (1988). Arthritis Rheum., 31, 315–324.

  • Asahara H, Fujisawa K, Kobata T, Hasunuma T, Maeda T, Asanuma M, Ogawa N, Inoue H, Sumida T and Nishioka K . (1997). Arthritis Rheum., 40, 912–918.

  • Broek D, Bartlett R, Crawford K and Nurse P . (1991). Nature, 349, 388–393.

  • Chinenov Y and Kerppola TK . (2001). Oncogene, 20, 2438–2454.

  • Fassbender HG . (1984). Arthritis Rheum., 27, 956.

  • Fassbender HG . (1998). Arth. Orthop. Trauma Surg., 117, 2–7.

  • Gould KL and Nurse P . (1989). Nature, 342, 39–45.

  • Hartwell LH and Kastan MB . (1994). Science, 266, 1821–1828.

  • Hino K, Shiozawa S, Kuroki Y, Ishikawa H, Shiozawa K, Sekiguchi K, Hirano H, Sakashita E, Miyashita K and Chihara K . (1995). Arthritis Rheum., 38, 678–683.

  • Hung TS, Kuo ML, Lin JK and Hsieh JSC . (1995). Cancer Lett., 96, 1–7.

  • Jacobs RA, Perrett D, Axon JM, Herbert KE and Scott DL . (1995). Clin. Exp. Rheumatol., 13, 717–723.

  • Kaker SS and Roy D . (1994). Cancer Lett., 87, 85–89.

  • Kawasaki H, Komai K, Ouyang Z, Murata M, Hikasa M, Ohgiri M and Shiozawa S . (2001). EMBO J., 20, 4618–4627.

  • Kawasaki H, Nakata Y, Suzuki G, Chihara K, Tokuhisa T and Shiozawa S . (1999). Int. Immunol., 11, 1873–1880.

  • Kuroki Y, Shiozawa S, Sugimoto T, Kanatani M, Kaji H, Miyachi A and Chihara K . (1994). Clin. Exp. Immunol., 95, 536–539.

  • Kuroki Y, Shiozawa S, Yoshihara R and Hotta H . (1993). J. Rheumatol., 20, 422–428.

  • Mohan R, Sivak J, Ashton P, Russo LA, Pham BQ, Kasahara N, Raizman MB and Fini ME . (2000). J. Biol. Chem., 275, 10405–10412.

  • Morgan DO . (1995). Nature, 374, 131–134.

  • Norbury C, Blow J and Nurse P . (1991). EMBO J., 10, 3321–3329.

  • Nurse P . (1990). Nature, 344, 503–508.

  • Piechaczyk M and Blanchard JM . (1994). Crit. Rev. Oncol. Hematol., 17, 93–131.

  • Pope RM, Lovis R, Mungre S, Perlman H, Koch AE and Haines III GK . (1999). Clin. Immunol., 91, 271–282.

  • Russell P and Nurse P . (1987). Cell, 49, 559–567.

  • Schaser K, Kinne RW, Beil H, Kladny B and Stoss H . (1996). Verh. Dtsch. Ges. Pathol., 80, 276–280.

  • Secchiero P, Bertolaso L, Casareto L, Gibellini D, Vitale M, Bemis K, Aleotti A, Capitani S, Franchini G, Gallo RC and Zauli G . (1998). Blood, 92, 1685–1696.

  • Shaulian E and Karin M . (2001). Oncogene, 20, 2390–2400.

  • Shiozawa S, Shimizu K, Tanaka K and Hino K . (1997). J. Clin. Invest., 99, 1210–1216.

  • Shiozawa S, Shiozawa K and Fujita T . (1983). Arthritis Rheum., 26, 472–478.

  • Shiozawa S, Tanaka Y, Fujita T and Tokuhisa T . (1992). J. Immunol., 148, 3100–3104.

  • Strausfeld U, Labbe JC, Fesquet D, Cavadore JC, Picard A, Sadhu K, Russell P and Doree M . (1991). Nature, 351, 242–245.

  • Trabant A, Aicher WK, Gay RE, Sukhatme VP, Fassbender HG and Gay S . (1992). Rheumatol. Int., 12, 53–59.

  • Wakisaka S, Suzuki N, Takeno M, Takebe Y, Nagafuchi H, Saito N, Hashimoto H, Tomita T, Ochi T and Sakane T . (1998). Ann. Rheum. Dis., 57, 487–497.

  • Yamanishi Y and Firestein GS . (2001). Rheum. Dis. Clin. North Am., 27, 355–371.

  • Zhang Y, Wang Z and Ravid K . (1996). J. Biol. Chem., 271, 4266–4271.

Download references

Acknowledgements

We thank Dr M Lamphier for critical reading of the manuscript. This work was supported in part by the grant-in-aid for scientific research to SS (B) 07557228, (B) 08457153, (B) 09470127 and (B) 11557026 of the Ministry of Education, Science, Sports and Culture.

Nucleotide data: Nucleotide sequence data of human wee1 promoter region are available in the DDBJ/EMBL/GenBank databases under the accession number AB019581.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Kobe University FHS School of Medicine, Kobe, 654-0142, Japan

    Hiroki Kawasaki, Koichiro Komai, Mikiko Nakamura, Eri Yamamoto, Zhufeng Ouyang, Toshie Nakashima, Tae Morisawa, Akira Hashiramoto, Hitoshi Ishikawa & Shunichi Shiozawa

  2. Rheumatic Disease Division, Kobe University Hospital, Kobe, 650-0017, Japan

    Akira Hashiramoto & Shunichi Shiozawa

  3. Department of Rheumatology, Konan Kakogawa Hospital, Kakogawa, 675-8545, Japan

    Kazuko Shiozawa

  4. Department of Orthopedic Surgery, Kobe University Hospital, Kobe, 650-0017, Japan

    Masahiro Kurosaka

Authors
  1. Hiroki Kawasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koichiro Komai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikiko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eri Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhufeng Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshie Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tae Morisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akira Hashiramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazuko Shiozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hitoshi Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masahiro Kurosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shunichi Shiozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shunichi Shiozawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kawasaki, H., Komai, K., Nakamura, M. et al. Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP-1: rheumatoid synovial cells overexpressing these genes go into aberrant mitosis. Oncogene 22, 6839–6844 (2003). https://doi.org/10.1038/sj.onc.1206903

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206903

Keywords

This article is cited by

Search

Advanced search

Quick links