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Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1.
Oncogene. 2004 Mar 04; 23(9):1656-67.O

Abstract

In cultured human dermal fibroblasts, transforming growth factor (TGF)-beta induced the mRNA expression of tenascin-C (TN-C). The molecular mechanism(s) underlying this process is not presently understood. In this study, we performed serial 5' deletion and a transient transfection analysis to define a region in the TN-C promoter mediating the inducible responsiveness to TGF-beta. This region contains an atypical nucleotide recognition element for the Smad family of transcriptional regulators. A DNA affinity precipitation assay revealed that Smad2/Smad3 bound to this site in a transient and specific manner. Overexpression of Smad3 or Smad4 activated the TN-C promoter activity and superinduced the TN-C promoter activity stimulated by TGF-beta. Moreover, simultaneous cotransfection of Smad3 and Smad4 activated the TN-C promoter activity in a synergistic manner. Mutation of the Smad-binding sites, the Ets-binding sites, or Sp1/3-binding sites in the TN-C promoter abrogated the TGF-beta/Smad-inducible promoter activity. Immunoprecipitation analysis revealed that Smad3, Sp1, and Ets1 form a transcriptionally active complex. Furthermore, the interaction between Smads and CBP/p300 in TGF-beta signaling was confirmed. These findings demonstrate the existence of a novel, functional binding element in the proximal region of the TN-C promoter mediating responsiveness to TGF-beta involving Smad3/4, Sp1, Ets1, and CBP/p300.

Authors+Show Affiliations

Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15001984

Citation

Jinnin, Masatoshi, et al. "Tenascin-C Upregulation By Transforming Growth Factor-beta in Human Dermal Fibroblasts Involves Smad3, Sp1, and Ets1." Oncogene, vol. 23, no. 9, 2004, pp. 1656-67.
Jinnin M, Ihn H, Asano Y, et al. Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1. Oncogene. 2004;23(9):1656-67.
Jinnin, M., Ihn, H., Asano, Y., Yamane, K., Trojanowska, M., & Tamaki, K. (2004). Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1. Oncogene, 23(9), 1656-67.
Jinnin M, et al. Tenascin-C Upregulation By Transforming Growth Factor-beta in Human Dermal Fibroblasts Involves Smad3, Sp1, and Ets1. Oncogene. 2004 Mar 4;23(9):1656-67. PubMed PMID: 15001984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1. AU - Jinnin,Masatoshi, AU - Ihn,Hironobu, AU - Asano,Yoshihide, AU - Yamane,Kenichi, AU - Trojanowska,Maria, AU - Tamaki,Kunihiko, PY - 2004/3/6/pubmed PY - 2004/3/26/medline PY - 2004/3/6/entrez SP - 1656 EP - 67 JF - Oncogene JO - Oncogene VL - 23 IS - 9 N2 - In cultured human dermal fibroblasts, transforming growth factor (TGF)-beta induced the mRNA expression of tenascin-C (TN-C). The molecular mechanism(s) underlying this process is not presently understood. In this study, we performed serial 5' deletion and a transient transfection analysis to define a region in the TN-C promoter mediating the inducible responsiveness to TGF-beta. This region contains an atypical nucleotide recognition element for the Smad family of transcriptional regulators. A DNA affinity precipitation assay revealed that Smad2/Smad3 bound to this site in a transient and specific manner. Overexpression of Smad3 or Smad4 activated the TN-C promoter activity and superinduced the TN-C promoter activity stimulated by TGF-beta. Moreover, simultaneous cotransfection of Smad3 and Smad4 activated the TN-C promoter activity in a synergistic manner. Mutation of the Smad-binding sites, the Ets-binding sites, or Sp1/3-binding sites in the TN-C promoter abrogated the TGF-beta/Smad-inducible promoter activity. Immunoprecipitation analysis revealed that Smad3, Sp1, and Ets1 form a transcriptionally active complex. Furthermore, the interaction between Smads and CBP/p300 in TGF-beta signaling was confirmed. These findings demonstrate the existence of a novel, functional binding element in the proximal region of the TN-C promoter mediating responsiveness to TGF-beta involving Smad3/4, Sp1, Ets1, and CBP/p300. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/15001984/Tenascin_C_upregulation_by_transforming_growth_factor_beta_in_human_dermal_fibroblasts_involves_Smad3_Sp1_and_Ets1_ L2 - https://doi.org/10.1038/sj.onc.1207064 DB - PRIME DP - Unbound Medicine ER -