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Regulation of the human transforming growth factor beta type II receptor gene promoter by novel Sp1 sites.
Oncogene. 2001 Oct 18; 20(47):6899-909.O

Abstract

The transforming growth factor-beta (TGF beta) type II receptor (T beta R-II) is responsible for transducing the growth inhibitory signals of TGF beta. The T beta R-II gene promoter lacks both a TATA box and a CAAT box near the transcription initiation site, and has been shown to contain binding sequences for several transcription factors (Sp1, AP1, NF-Y, Cut and ERT) which are important for T beta R-II gene promoter activity in vitro. However, it is still not clear which interactions are important for the regulation of T beta R-II gene promoter activity in vivo. Using in vivo genomic DNA footprinting of normal human epithelial cells (HaCaT), we have identified two novel identical and strongly protected sites (ggggctgg) at positions -59 and -102 of the T beta R-II gene promoter. Mutation of either site significantly reduced promoter activity in transient transfections. Protein binding to these sites, as determined by electrophoretic mobility shift assays (EMSA), was specifically competed with consensus Sp1 oligonucleotides. Furthermore, anti-Sp1/3 antibodies produced band shifts when incubated with the T beta R-II -59 and -102 DNA probes. Importantly, Sp1 protein binding was influenced by the presence of an intact NF-Y binding site at position -83. Our data suggests that both Sp1 and NF-Y may play an important role in regulating T beta R-II gene promoter basal activity in vivo.

Authors+Show Affiliations

Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Oncology, University of South Florida, Tampa, Florida, FL 33612, USA.No 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

11687969

Citation

Jennings, R, et al. "Regulation of the Human Transforming Growth Factor Beta Type II Receptor Gene Promoter By Novel Sp1 Sites." Oncogene, vol. 20, no. 47, 2001, pp. 6899-909.
Jennings R, Alsarraj M, Wright KL, et al. Regulation of the human transforming growth factor beta type II receptor gene promoter by novel Sp1 sites. Oncogene. 2001;20(47):6899-909.
Jennings, R., Alsarraj, M., Wright, K. L., & Muñoz-Antonia, T. (2001). Regulation of the human transforming growth factor beta type II receptor gene promoter by novel Sp1 sites. Oncogene, 20(47), 6899-909.
Jennings R, et al. Regulation of the Human Transforming Growth Factor Beta Type II Receptor Gene Promoter By Novel Sp1 Sites. Oncogene. 2001 Oct 18;20(47):6899-909. PubMed PMID: 11687969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of the human transforming growth factor beta type II receptor gene promoter by novel Sp1 sites. AU - Jennings,R, AU - Alsarraj,M, AU - Wright,K L, AU - Muñoz-Antonia,T, PY - 2001/03/15/received PY - 2001/06/14/revised PY - 2001/07/05/accepted PY - 2001/11/1/pubmed PY - 2002/1/5/medline PY - 2001/11/1/entrez SP - 6899 EP - 909 JF - Oncogene JO - Oncogene VL - 20 IS - 47 N2 - The transforming growth factor-beta (TGF beta) type II receptor (T beta R-II) is responsible for transducing the growth inhibitory signals of TGF beta. The T beta R-II gene promoter lacks both a TATA box and a CAAT box near the transcription initiation site, and has been shown to contain binding sequences for several transcription factors (Sp1, AP1, NF-Y, Cut and ERT) which are important for T beta R-II gene promoter activity in vitro. However, it is still not clear which interactions are important for the regulation of T beta R-II gene promoter activity in vivo. Using in vivo genomic DNA footprinting of normal human epithelial cells (HaCaT), we have identified two novel identical and strongly protected sites (ggggctgg) at positions -59 and -102 of the T beta R-II gene promoter. Mutation of either site significantly reduced promoter activity in transient transfections. Protein binding to these sites, as determined by electrophoretic mobility shift assays (EMSA), was specifically competed with consensus Sp1 oligonucleotides. Furthermore, anti-Sp1/3 antibodies produced band shifts when incubated with the T beta R-II -59 and -102 DNA probes. Importantly, Sp1 protein binding was influenced by the presence of an intact NF-Y binding site at position -83. Our data suggests that both Sp1 and NF-Y may play an important role in regulating T beta R-II gene promoter basal activity in vivo. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11687969/Regulation_of_the_human_transforming_growth_factor_beta_type_II_receptor_gene_promoter_by_novel_Sp1_sites_ L2 - https://doi.org/10.1038/sj.onc.1204808 DB - PRIME DP - Unbound Medicine ER -