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:

Alteration of cell adhesion and cell cycle properties of ES cells by an inducible dominant interfering Myb mutant

Oncogene volume 20, pages 1425–1434 (2001)Cite this article

Abstract

The Myb transcription factors, c-Myb, A-Myb, and B-Myb, regulate cell differentiation and/or proliferation. To investigate the role of B-Myb in embryogenesis, we introduced an inducible dominant interfering Myb protein (MERT) into embryonic stem (ES) cells, which express B-Myb as an exclusive member of Myb family. Disruption of normal B-Myb function by the conditional activation of MERT caused a drastic morphological alteration of ES cells and G1-S cell cycle arrest. The inhibition of B-Myb function by MERT dissociated tightly packed ES cell colonies into dispersed single cells that subsequently detached from the culture dish. Cell adhesion analyses revealed that suppression of B-Myb function reduced the adhesion with extracellular matrix proteins, such as laminin, collagen, and fibronectin. This reduction was presumably due to decreased cell surface expression of β1 integrin. Embryoid body formation was also severely retarded by the activation of MERT. This impairment was attributed to reduced expression of E-cadherin, which functions as a homophilic intercellular adhesion molecule. Simultaneously, blocking B-Myb function did not alter the expression of differentiation markers. Our data indicate that B-Myb plays important roles in regulating cell adhesion and cell cycle progression. These results are well consistent with the recent report on the phenotype of B-Myb null mice and show that the regulation of cell adhesion is an important B-Myb function that has not yet been assumed.

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
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Arsura M, Introna M, Passerini F, Mantovani A, Golay J . 1992 Blood 79: 2708–2716

  • Badiani P, Corbella P, Kioussis D, Marvel J, Weston K . 1994 Genes Dev. 8: 770–782

  • Bellis SL, Newman E, Friedman EA . 1999 J. Cell. Physiol. 181: 33–44

  • Bradley A, Evans M, Kaufman MH, Robertson E . 1984 Nature 309: 255–256

  • Fahraeus R, Lane DP . 1999 EMBO J. 18: 2106–2118

  • Fassler R, Meyer M . 1995 Genes Dev. 9: 1896–1908

  • Fassler R, Pfaff M, Murphy J, Noegel AA, Johansson S, Timpl R, Albrecht R . 1995 J. Cell. Biol. 128: 979–988

  • Frampton J, McNagny K, Sieweke M, Philip A, Smith G, Graf T . 1995 EMBO J. 14: 2866–2875

  • Frampton J, Ramqvist T, Graf T . 1996 Genes Dev. 10: 2720–2731

  • Giancotti FG, Ruoslahti E . 1999 Science 285: 1028–1032

  • Ginsberg MH, Du X, Plow EF . 1992 Curr. Opin. Cell. Biol. 4: 766–771

  • Joyner AL . 1993 IRL Press 142: 1121–1133

  • Krude T . 1999 Exp. Cell. Res. 247: 148–159

  • Kume A, Hashiyama M, Suda T, Ozawa K . 1999 Stem Cells 17: 226–232

  • Larue L, Antos C, Butz S, Huber O, Delmas V, Dominis M, R K . 1996 Development 122: 3185–3194

  • Levenberg S, Yarden A, Kam Z, Geiger B . 1999 Oncogene 18: 869–876

  • Lipsick JS . 1996 Oncogene 13: 223–235

  • Littlewood TD, Hancock DC, Danielian PS, Parker MG, Evan GI . 1995 Nucleic Acids Res. 23: 1686–1690

  • Liu ZJ, Tanaka Y, Mine S, Morinobu A, Yagita H, Okumura K, Taniguchi T, Yamamura H, Minami Y . 1998 Blood 92: 4700–4711

  • Lyon JJ, Watson RJ . 1996 Gene 182: 123–128

  • Manabe R, Oh-e N, Sekiguchi K . 1999 J. Biol. Chem. 274: 5919–5924

  • Martin GR . 1981 Proc. Natl. Acad. Sci. USA 78: 7634–7638

  • Mucenski ML, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott WJJ, Potter SS . 1991 Cell 65: 677–689

  • Ness SA . 1999 Oncogene 18: 3039–3046

  • Nomura N, Takahashi M, Matsui M, Ishii S, Date T, Sasamoto S, Ishizaki R . 1988 Nucleic Acids Res. 16: 11075–11089

  • Oppenheimer DG, Herman PL, Sivakumaran S, Esch J, Marks MD . 1991 Cell 67: 483–493

  • Priddle H, Hemmings L, Monkley S, Woods A, Patel B, Sutton D, Dunn GA, Zicha D, Critchley DR . 1998 J. Cell. Biol. 142: 1121–1133

  • Riethmacher D, Brinkmann V, Birchmeier C . 1995 Proc. Natl. Acad. Sci. USA 92: 855–859

  • Saitou M, Sugai S, Tanaka T, Shimouchi K, Fuchs E, Narumiya S, Kakizuka A . 1995 Nature 374: 159–162

  • Sala A, Calabretta B . 1992 Proc. Natl. Acad. Sci. USA 89: 10415–10419

  • Sala A, Casella I, Bellon T, Calabretta B, Watson RJ, Peschle C . 1996 J. Biol. Chem. 271: 9363–9367

  • Sitzmann J, Noben-Trauth K, Kamano H, Klempnauer KH . 1996 Oncogene 12: 1889–1894

  • Takahashi T, Suwabe N, Dai P, Yamamoto M, Ishii S, Nakano T . 2000 Oncogene 19: 134–140

  • Tanaka Y, Patestos NP, Maekawa T, Ishii S . 1999 J. Biol. Chem. 274: 28067–28070

  • Taylor D, Badiani P, Weston K . 1996 Genes Dev. 10: 2732–2744

  • Toscani A, Mettus RV, Coupland R, Simpkins H, Litvin J, Orth J, Hatton KS, Reddy EP . 1997 Nature 386: 713–717

  • Westin EH, Gallo RC, Arya SK, Eva A, Souza LM, Baluda MA, Aaronson SA, Wong-Staal F . 1982 Proc. Natl. Acad. Sci. USA 79: 2194–2198

  • Weston K . 1998 Curr. Opin. Genet. Dev. 8: 76–81

  • White JR, Weston K . 2000 Oncogene 19: 1196–1205

  • Wiles MV . 1993 Methods Enzymol. 225: 900–918

  • Zhao JH, Reiske H, Guan JL . 1998 J. Cell. Biol. 143: 1997–2008

Download references

Acknowledgements

We thank Drs K Weston, H Yagita, S Ishii and A Kume for gifting us various reagents and useful discussion. This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japanese Society for Promotion of Sciences (JSPS-RFTF98L01101), and the Cell Science Research Foundation.

Author information

Authors and Affiliations

  1. Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, 565-0871, Osaka, Japan

    Naomi Iwai, Kenji Kitajima, Katsuya Sakai, Tohru Kimura & Toru Nakano

Authors
  1. Naomi Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Kitajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsuya Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tohru Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toru Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwai, N., Kitajima, K., Sakai, K. et al. Alteration of cell adhesion and cell cycle properties of ES cells by an inducible dominant interfering Myb mutant. Oncogene 20, 1425–1434 (2001). https://doi.org/10.1038/sj.onc.1204236

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204236

Keywords

This article is cited by

Search

Advanced search

Quick links