Increased expression of TATA-binding protein, the central transcription factor, can contribute to oncogenesis

Sandra A S Johnson, Louis Dubeau, Michael Kawalek, Andrew Dervan, Axel H. Schönthal, Chi V. Dang, Deborah L. Johnson

Research output: Contribution to journalArticle

Abstract

Despite the central role of TATA-binding protein (TBP) in transcription, changes in cellular TBP concentration produce selective effects on gene expression. Moreover, TBP is up-regulated by oncogenic signaling pathways. These findings suggest that TBP could be a nexus in pathways that regulate cell proliferation and that genetic lesions that result in cellular transformation may produce their effects at least in part through TBP. We provide evidence consistent with this hypothesis, demonstrating that increases in TBP expression contribute to cellular transformation. A Ras-mediated increase in TBP expression is required for full Ras transforming activity. TBP overexpression induces cells to grow in an anchorage-independent manner and to form tumors in athymic mice. These effects on cellular transformation require changes in RNA polymerase II-dependent transcription and on the selective recruitment of TBP to promoters via its DNA binding activity. TBP expression is elevated in human colon carcinomas relative to normal colon epithelium. Both Rasdependent and Ras-independent mechanisms mediate increases in TBP expression in colon carcinoma cell lines. We conclude that TBP may be a critical component in dysregulated signaling that occurs downstream of genetic lesions that cause tumors.

Original languageEnglish (US)
Pages (from-to)3043-3051
Number of pages9
JournalMolecular and Cellular Biology
Volume23
Issue number9
DOIs
Publication statusPublished - May 2003

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Johnson, S. A. S., Dubeau, L., Kawalek, M., Dervan, A., Schönthal, A. H., Dang, C. V., & Johnson, D. L. (2003). Increased expression of TATA-binding protein, the central transcription factor, can contribute to oncogenesis. Molecular and Cellular Biology, 23(9), 3043-3051. https://doi.org/10.1128/MCB.23.9.3043-3051.2003