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J Biol Chem, Vol. 273, Issue 11, 6203-6209, March 13, 1998
Identification of Redox-sensitive Cysteines in GA-binding
Protein- That Regulate DNA Binding and
Heterodimerization
Yurii
Chinenov,
Tonya
Schmidt,
Xiu-Ying
Yang, and
Mark E.
Martin
From the Department of Biochemistry, University of Missouri at
Columbia, Columbia, Missouri 65212
The transcription factor GA-binding protein
(GABP) is composed of two subunits, GABP and GABP . The
DNA-binding subunit, GABP , is a member of the Ets family of
transcription factors, characterized by the conserved Ets-domain that
mediates DNA binding and associates with GABP , which lacks a
discernible DNA binding domain, through ankyrin repeats in the
NH2 terminus of GABP . We previously demonstrated
that GABP is subject to redox regulation in vitro and
in vivo through four COOH-terminal cysteines in GABP . To
determine the roles of individual cysteines in GABP redox regulation, we generated a series of serine substitution mutants by site-directed mutagenesis and identified three redox-sensitive cysteine residues in
GABP (Cys388, Cys401, and
Cys421). Sulfhydryl modification of Cys388 and
Cys401 inhibits DNA binding by GABP , whereas,
modification of Cys421 has no effect on GABP DNA binding
but inhibits dimerization with GABP . The positions of
Cys388 and Cys401 within the known Ets-domain
structure suggest two very different mechanisms for redox regulation of
DNA binding. Sulfhydryl modification of Cys388 could
directly interfere with DNA binding or might alter the positioning of
the DNA-binding helix 3. Modification of Cys401 may inhibit
DNA binding through stabilization of an inhibitory helix similar to
that described in the Ets-1 protein. Thus, GABP is regulated through at
least two redox-sensitive activities, DNA binding and
heterodimerization.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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