HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An addition or correction has been published Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chinenov, Y. Articles by Martin, M. E. Search for Related Content PubMed PubMed Citation Articles by Chinenov, Y. Articles by Martin, M. E. Social Bookmarking                      What's this?

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

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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. S. Ayene, T. D. Stamato, S. K. Mauldin, J. E. Biaglow, S. W. Tuttle, S. F. Jenkins, and C. J. Koch Mutation in the Glucose-6-phosphate Dehydrogenase Gene Leads to Inactivation of Ku DNA End Binding during Oxidative Stress J. Biol. Chem., March 15, 2002; 277(12): 9929 - 9935. [Abstract] [Full Text] [PDF]

				J. M. Weitzel, C. Radtke, and H. J. Seitz Two thyroid hormone-mediated gene expression patterns in vivo identified by cDNA expression arrays in rat Nucleic Acids Res., December 15, 2001; 29(24): 5148 - 5155. [Abstract] [Full Text] [PDF]

				H. E. MARSHALL, K. MERCHANT, and J. S. STAMLER Nitrosation and oxidation in the regulation of gene expression FASEB J, October 1, 2000; 14(13): 1889 - 1900. [Abstract] [Full Text]

				K. Aurrekoetxea-Hernández and E. Buetti Synergistic Action of GA-Binding Protein and Glucocorticoid Receptor in Transcription from the Mouse Mammary Tumor Virus Promoter J. Virol., June 1, 2000; 74(11): 4988 - 4998. [Abstract] [Full Text]

				Y. Chinenov, M. Henzl, and M. E. Martin The alpha and beta Subunits of the GA-binding Protein Form a Stable Heterodimer in Solution. REVISED MODEL OF HETEROTETRAMERIC COMPLEX ASSEMBLY J. Biol. Chem., March 10, 2000; 275(11): 7749 - 7756. [Abstract] [Full Text] [PDF]

				C. C. Jao, M. K. Weidman, A. R. Perez, and E. Gharakhanian Cys9, Cys104 and Cys207 of simian virus 40 Vp1 are essential for inter-pentamer disulfide-linkage and stabilization in cell-free lysates J. Gen. Virol., September 1, 1999; 80(9): 2481 - 2489. [Abstract] [Full Text]

				Q. Gong, L. J. Brown, and M. J. MacDonald Functional Analysis of Two Promoters for the Human Mitochondrial Glycerol Phosphate Dehydrogenase Gene J. Biol. Chem., November 22, 2000; 275(48): 38012 - 38021. [Abstract] [Full Text] [PDF]