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.

  • Short Report
  • Published:

Cross-regulatory interaction between Stra13 and USF results in functional antagonism

Oncogene volume 20, pages 4750–4756 (2001)Cite this article

Abstract

Transcription factors belonging to the basic helix–loop–helix (bHLH) family are critical regulators of cellular proliferation and differentiation. The functional activity of these proteins can be regulated by heterodimerization through the HLH domain, as a result of formation of functional or non-functional heterodimers. The presence of a leucine zipper in bHLH-leucine zipper (bHLHZip) proteins, however, prevents such heterodimeric interactions via the HLH domain between bHLH and bHLHZip proteins. To identify cellular proteins that directly interact with and modulate transcriptional repression mediated by the bHLH protein Stra13, we carried out a yeast two hybrid screen. The bHLHZip protein USF (Upstream Stimulatory factor) was identified as a Stra13 interacting protein. We demonstrate a direct interaction between Stra13 and USF that is dependent upon the C-terminal repression domain of Stra13 and the DNA-binding domain of USF. Stra13 and USF also colocalize and functionally interact in mammalian cells. Co-expression of USF abrogates Stra13-mediated repression of target genes and conversely, Stra13 inhibits DNA-binding and USF-mediated transactivation. Taken together, our data demonstrate that Stra13 and USF interact physically and functionally, and identify a novel mode of cross regulatory interaction between members of the bHLH and bHLHZip families that abrogates their functional activity.

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

Similar content being viewed by others

References

  • Boudjelal M, Taneja R, Matsubara S, Bouillet P, Dollé P, Chambon P . 1997 Genes Dev. 11: 2052–2065

  • Carthew RW, Chodosh LA, Sharp PA . 1985 Cell 43: 439–448

  • Cvekl A, Sax CM, Bresnick EH, Piatigorsky J . 1994 Mol. Cell. Biol. 14: 7363–7376

  • Dang CV . 1999 Mol. Cell. Biol. 19: 1–11

  • Fisher A, Caudy M . 1998 Bioessays 20: 298–306

  • James P, Halladay J, Craig EA . 1996 Genetics 144: 1425–1436

  • Lee TC, Ziff EB . 1999 J. Biol. Chem. 274: 595–606

  • Luo X, Sawadogo M . 1996a Proc. Natl. Acad. Sci. USA 93: 1308–1313

  • Luo X, Sawadogo M . 1996b Mol. Cell. Biol. 16: 1367–1375

  • Massari ME, Murre C . 2000 Mol. Cell. Biol. 20: 429–440

  • Miyamoto NG, Moncollin V, Egly JM, Chambon P . 1985 EMBO J. 4: 3563–3570

  • Navankasattusas S, Sawadogo M, van Bilsen M, Dang CV, Chien KR . 1994 Mol. Cell. Biol. 14: 7331–7339

  • Pognonec P, Boulukos KE, Aperlo C, Fujimoto M, Ariga H, Nomoto A, Kato H . 1997 Oncogene 14: 2091–2098

  • Rao E, Dang W, Tian G, Sen R . 1997 J. Biol. Chem. 272: 6722–6732

  • Sasai Y, Kageyama R, Tagawa Y, Shigemoto R, Nakanishi S . 1992 Genes. Dev. 12: 2620–2634

  • Sawadogo M, Roeder RG . 1985 Cell 43: 165–175

  • Sieweke MH, Tekotte H, Jarosch U, Graf T . 1998 EMBO J. 17: 1728–1739

  • Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M . 1992 Gene. Exp. 2: 231–240

  • Sirito M, Lin Q, Deng JM, Behringer RR, Sawadogo M . 1998 Proc. Natl. Acad. Sci. USA 95: 3758–3763

  • Sun H, Taneja R . 2000 Proc. Natl. Acad. Sci. USA 97: 4058–4063

  • Sun XH, Copeland NC, Jenkins NA, Baltimore D . 1991 Mol. Cell. Biol. 11: 5603–5611

  • Timchenko N, Wilson DR, Taylor LR, Abdelsayed S, Wilde M, Sawadogo M, Darlington GJ . 1995 Mol. Cell. Biol. 15: 1192–1202

  • Vallet VS, Casado M, Henrion AA, Bucchini D, Raymondjean M, Kahn A, Vaulont S . 1998 J. Biol. Chem. 273: 20175–20179

  • Viollet B, Lefrancois-Martinez A, Henrion A, Kahn A, Raymondjean M, Martinez A . 1996 J. Biol. Chem. 271: 1405–1415

  • Wallin JJ, Rinkenberger JL, Rao S, Gackstetter ER, Koshland ME, Zwollo P . 1999 J. Biol. Chem. 274: 15959–15965

Download references

Acknowledgements

We are grateful to P Chambon, M Sawadogo, M Raymondjean, P James, D Sassoon, J Licht, D Ayer and E Ziff for the gift of various reagents and K Borden for advice on immunofluorescence studies. We thank R Gopalkrishnan and J Bieker for comments on the manuscript. This work was supported in part by funds from the NIH, March of Dimes and Waxman Cancer Research Foundation (R Taneja).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, 10029-6574, NY, USA

    Manya Dhar & Reshma Taneja

Authors
  1. Manya Dhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reshma Taneja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reshma Taneja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dhar, M., Taneja, R. Cross-regulatory interaction between Stra13 and USF results in functional antagonism. Oncogene 20, 4750–4756 (2001). https://doi.org/10.1038/sj.onc.1204637

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204637

Keywords

This article is cited by

Search

Advanced search

Quick links