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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,
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.

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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