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Molecular and Cellular Biology, May 2003, p. 3043-3051, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3043-3051.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Increased Expression of TATA-Binding Protein, the Central Transcription Factor, Can Contribute to Oncogenesis

Sandra A. S. Johnson,1 Louis Dubeau,2 Michael Kawalek,1 Andrew Dervan,1 Axel H. Schönthal,3 Chi V. Dang,4 and Deborah L. Johnson1*

Department of Biochemistry and Molecular Biology,1 Department of Pathology,2 Department of Microbiology and Immunology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033,3 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 212054

Received 19 December 2002/ Returned for modification 31 January 2003/ Accepted 12 February 2003

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 Ras-dependent 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.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, 1985 Zonal Ave., PSC-402, Los Angeles, CA 90033. Phone: (323) 442-1446. Fax: (323) 442-1681. E-mail: johnsond{at}usc.edu.

Molecular and Cellular Biology, May 2003, p. 3043-3051, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3043-3051.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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