Skip to main content
Log in

Tsc-22 enhances TGF-β signaling by associating with Smad4 and induces erythroid cell differentiation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Tsc-22 was isolated as a TGF-β-inducible gene by differential screening of the mouse osteoblastic cell cDNA library [J Biol Chem 267 (1992) 10219]. tsc-22 mRNA is expressed in almost all organs of mice and humans and its expression is induced in a variety of cell lines by many different factors including TGF-β, phorbol ester, serum, and progestin. tsc-22 encodes a 18-kd protein that contains a leucine zipper motif and a Tsc-box. The leucine zipper motif of the Tsc-22 protein does not have a basic DNA binding motif and when the protein was fused to a heterologous DNA binding domain, it showed various transcription-modulating activities ranging from activation to repression [J Biol Chem 274 (1999) 27439, Biochem Biophys Res Commun 278 (2000) 659]. Although these results suggest that the Tsc-22 protein functions as a transcriptional regulator recruiting various coactivators or repressors, its mechanism is not known. In this study, we examined whether Tsc-22 modulates the TGF-β-dependant signaling pathway and found that Tsc-22 binds to and modulate the transcriptional activity of Smad3 and Smad4. Its effect on cellular differentiation was also examined. (Mol Cell Biochem 271: 23–28, 2005)

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Shibanuma M, Kuroki T, Nose K: Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. J Biol Chem 267: 10219–10224, 1992

    Google Scholar 

  2. Kester HA, Blanchetot C, den Hertog J, van der Saag PT, van der Burg B: Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine-zipper proteins that can homodimerize and heterodimerize and has transcriptional repressor activity. J Biol Chem 274: 27439–27447, 1999

    Google Scholar 

  3. Hino S, Kawamata H, Uchida D, Omotehara F, Miwa Y, Begum NM, Yoshida H, Fujimori T, Sato M: Nuclear translocation of Tsc-22 concomitant with apoptosis: Tsc-22 as a putative transcriptional regulator. Biochem Biophys Res Commun 278: 659–664, 2000

    Google Scholar 

  4. Massague J, Wotton D: Transcriptional control by the TGF-β/Smad signaling system. EMBO J 19: 1745–1754, 2000

    Article  CAS  PubMed  Google Scholar 

  5. Itoh S, Itoh F, Goumans M, ten Dijke P: Signaling of transforming growth factor-β family members through Smad proteins. Eur J Biochem 267: 6954–6967, 2000

    Google Scholar 

  6. Oft M, Peli J, Rudaz C, Schwartz H, Beug H, Reichmann E: Tgf-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumors. Genes Dev 10: 2462–2477, 1996

    CAS  PubMed  Google Scholar 

  7. Feng XH, Zhang Y, Wu RY, Derynck R: The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation. Genes Dev 12: 2153–2163, 1998

    Google Scholar 

  8. Janknecht R, Wells NJ, Hunter T: TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. Genes Dev 12: 2144–2119, 1998

    Google Scholar 

  9. Nishihara A, Hanai J, Okamoto N, Yanagisawa J, Kato S, Miyazono K, Kawabata M: Role of p300, a transcriptional coactivator, in signalling of TGF-beta. Genes Cells 3: 613–623, 1998

    Google Scholar 

  10. Pouponnot C, Jayaraman L, Massague J: Physical and functional interaction of SMADs and p300/CBP. J Biol Chem 273: 22865–22868, 1998

    Google Scholar 

  11. Shen X, Hu PP, Liberati NT, Datto MB, Frederick JP, Wang XF: TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol Biol Cell 9: 3309–3319, 1998

    Google Scholar 

  12. Topper JN, DiChiara MR, Brown JD, Williams AJ, Falb D, Collins T, Gimbrone MA, Jr: CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor beta transcriptional responses in endothelial cells. Proc Natl Acad Sci USA 95: 9506–9511, 1998

    Google Scholar 

  13. Wotton D, Lo RS, Lee S, Massague J: A Smad transcriptional corepressor Cell 97: 29–39, 1999

    Google Scholar 

  14. Akiyoshi S, Inoue H, Hanai J, Kusanagi K, Nemoto N, Miyazono K, Kawabata M: c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads. J Biol Chem 274: 35269–35277, 1999

    Google Scholar 

  15. Luo K, Stroschein SL, Wang W, Chen D, Martens E, Zhou S, Zhou Q: The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev 13: 2196–2206, 1999

    Google Scholar 

  16. Sun Y, Liu X, Eaton EN, Lane WS, Lodish HF, Weinberg RA: Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling. Mol Cell 4: 499–509, 1999

    Article  CAS  PubMed  Google Scholar 

  17. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K: Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science 286: 771–774, 1999

    Article  CAS  PubMed  Google Scholar 

  18. Vogel P, Magert HJ, Cieslak A, Adermann K, Forssmann WG: hDIP—A potential transcriptional regulator related to murine TSC-22 and Drosophila shortsighted (shs)—is expressed in a large number of human tissues. Biochim Biophys Acta 1309: 200–204, 1996

    Google Scholar 

  19. Treisman JE, Lai ZC, Rubin GM: Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-beta-responsive gene. Development 121: 2835–2845, 1995

    Google Scholar 

  20. de Caestecker MP, Yahata T, Wang D, Parks WT, Huang S, Hill CS, Shioda T, Roberts AB, Lechleider RJ: The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J Biol Chem 275: 2115–2122, 2000

    Google Scholar 

  21. Shin HM, Seoh JY, Chung HY, Choi SJ, Hahn MJ, Kang JS, Choi MS, Han TH: Requirement of MEF2D in the induced differentiation of HL60 promyeloid cells. Mol Immunol 36: 1209–1214, 1999

    Google Scholar 

  22. Taketani S, Furukawa T, Furuyama K: Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells. Eur J Biochem 268: 1705–1711, 2001

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, SJ., Moon, JH., Ahn, YW. et al. Tsc-22 enhances TGF-β signaling by associating with Smad4 and induces erythroid cell differentiation. Mol Cell Biochem 271, 23–28 (2005). https://doi.org/10.1007/s11010-005-3456-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-3456-7

Key words

Navigation