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Cell Growth & Differentiation, Vol 6, Issue 6 719-726, Copyright © 1995 by American Association of Cancer Research
ARTICLES |
S Hirsch and WK Miskimins
Department of Biochemistry and Molecular Biology, University of South Dakota, School of Medicine, Vermillion 57069, USA.
Activation of the human transferrin receptor promoter by mitogenic stimulation of quiescent cells is a delayed event that reaches a maximum several hours after stimulation. Previous results have defined a region of the transferrin receptor gene promoter that is required for increased expression in mitogen-activated cells (W. K. Miskimins and D. B. Brown, Exp. Cell Res., 191: 328-331, 1990; Q. Ouyang et al., Mol. Cell. Biol., 13: 1796-1804, 1993). This region contains two elements (elements A and B) that appear to cooperate in the response to mitogenic stimulation. Serum stimulation of quiescent cells leads to the induction of nuclear factors that bind to both the A and B elements. Induction of these factors is also a delayed response to serum stimulation and reaches a maximum 6-9 h after stimulation. Element A, which is an unusual GC-rich sequence, forms several serum-inducible DNA-protein complexes, all of which depend on contacts within GC boxes. A major inducible complex of element A contains a factor that is supershifted by antibodies against the transcription factor Sp1. The B element appears to have overlapping binding sites for two types of factors. One of these sites binds factors that are competed off by an AP-1 consensus-binding site. The other B element site binds inducible factors that interact with GC boxes, identical to those observed for element A.
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