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PMID: 8417326 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity.

Molecular and cellular biology ·Vol. 13 ·No. 1 ·1993-01-00 ·Pages 196-206

Veals SA, Santa Maria T, Levy DE

Abstract

Alpha interferon (IFN-alpha) induces the transcription of a large set of genes through activation of multimeric transcription factor ISGF3. This factor can be dissociated into two protein components, termed ISGF3 gamma and ISGF3 alpha. ISGF3 gamma is a 48-kDa protein related at the amino terminus to members of the IFN-regulatory factor (IRF) and Myb families of DNA-binding proteins; ISGF3 alpha consists of three polypeptides of 84, 91, and 113 kDa that self-assemble to form an activated component in response to IFN-alpha. DNA-binding studies indicated that ISGF3 gamma binds DNA alone, recognizing the IFN-stimulated response element, while the ISGF3 alpha polypeptides alone display no specific interactions with DNA. A complex between ISGF3 gamma and activated ISGF3 alpha binds the IFN-stimulated response element with much greater affinity than does the 48-kDa ISGF3 gamma protein alone. The DNA-binding domain of ISGF3 gamma and regions responsible for protein-protein interaction with ISGF3 alpha were identified by using deleted forms of ISGF3 gamma expressed in vitro. The amino-terminal region of ISGF3 gamma homologous to the IRF and Myb proteins was sufficient for interaction with DNA and displayed the binding specificity of the intact protein; phosphorylation of this region was necessary for activity. A second region of 160 amino acids separated from the DNA-binding domain by over 100 amino acids contained a domain capable of associating with ISGF3 alpha and was sufficient to confer specific ISGF3 alpha interaction to a heterologous protein. Interaction of the ISGF3 alpha component with the protein interaction domain of ISGF3 gamma altered the DNA-binding specificity of the resulting complex, suggesting that one or more of the ISGF3 alpha polypeptides make base-specific contacts with DNA. This interaction defines a mechanism through which IRF-like proteins complexed with regulatory components can display novel DNA-binding specificities.

MeSH Terms
Base Sequence Binding Sites DNA-Binding Proteins/chemistry,metabolism HeLa Cells Humans Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, alpha Subunit Interferon-Stimulated Gene Factor 3, gamma Subunit Macromolecular Substances Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides/chemistry Protein Binding Recombinant Proteins/metabolism Sequence Deletion Structure-Activity Relationship Transcription Factors/chemistry,metabolism
Chemicals
DNA-Binding Proteins IRF9 protein, human Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, alpha Subunit Interferon-Stimulated Gene Factor 3, gamma Subunit Macromolecular Substances Oligodeoxyribonucleotides Recombinant Proteins Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Veals S A
Department of Pathology, New York University School of Medicine, New York 10016.
Santa Maria T
Levy D E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.1.196-206.1993
Published
1993-01-00
Pages
196-206
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358899
Subset
IM
Grants
NIGMS NIH HHS · 5T32-GM07308 · United States
NIAID NIH HHS · AI28900 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.1.196-206.1993 PMC Full Text View journal details
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