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Molecular and Cellular Biology, February 1999, p. 1508-1517, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cell-Type-Dependent Activity of the Ubiquitous Transcription Factor USF in Cellular Proliferation and Transcriptional Activation

Yibing Qyang,1 Xu Luo,1,dagger Tao Lu,1 Preeti M. Ismail,1 Dmitry Krylov,2 Charles Vinson,2 and Michèle Sawadogo1,*

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030,1 and Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 208922

Received 29 September 1997/Returned for modification 8 November 1997/Accepted 4 November 1998

USF1 and USF2 are basic helix-loop-helix transcription factors implicated in the control of cellular proliferation. In HeLa cells, the USF proteins are transcriptionally active and their overexpression causes marked growth inhibition. In contrast, USF overexpression had essentially no effect on the proliferation of the Saos-2 osteosarcoma cell line. USF1 and USF2 also lacked transcriptional activity in Saos-2 cells when assayed by transient cotransfection with USF-dependent reporter genes. Yet, there was no difference in the expression, subcellular localization, or DNA-binding activity of the USF proteins in HeLa and Saos-2 cells. Furthermore, Gal4-USF1 and Gal4-USF2 fusion proteins activated transcription similarly in both cell lines. Mutational analysis and domain swapping experiments revealed that the small, highly conserved USF-specific region (USR) was responsible for the inactivity of USF in Saos-2 cells. In HeLa, the USR serves a dual function. It acts as an autonomous transcriptional activation domain at promoters containing an initiator element and also induces a conformational change that is required for USF activity at promoters lacking an initiator. Taken together, these results suggest a model in which the transcriptional activity of the USF proteins, and consequently their antiproliferative activity, is tightly controlled by interaction with a specialized coactivator that recognizes the conserved USR domain and, in contrast to USF, is not ubiquitous. The activity of USF is therefore context dependent, and evidence for USF DNA-binding activity in particular cells is insufficient to indicate USF function in transcriptional activation and growth control.


* Corresponding author. Mailing address: Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: (713) 794-1281. Fax: (713) 794-4295. E-mail: msawadog{at}notes.mdacc.tmc.edu.

dagger Present address: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75235.


Molecular and Cellular Biology, February 1999, p. 1508-1517, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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