Architecture of high mobility group protein I-C.DNA complex and its perturbation upon phosphorylation by Cdc2 kinase

The high mobility group I-C (HMGI-C) protein is an abundant component of rapidly proliferating undifferentiated cells. High level expression of this protein is characteristic for early embryonic tissue and diverse tumors. HMGI-C can function as an architectural factor enhancing the activity of trans...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-01, Vol.275 (3), p.1793
Main Authors: Schwanbeck, R, Manfioletti, G, Wiśniewski, J R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
CDC2 Protein Kinase - chemistry
CDC2 Protein Kinase - metabolism
DNA - metabolism
DNA Footprinting
Dose-Response Relationship, Drug
High Mobility Group Proteins - chemistry
High Mobility Group Proteins - genetics
High Mobility Group Proteins - metabolism
HMGA2 Protein
Interferon-beta - genetics
Interferon-beta - metabolism
Methylation
Mice
Models, Genetic
Molecular Sequence Data
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Protein Conformation
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Summary:The high mobility group I-C (HMGI-C) protein is an abundant component of rapidly proliferating undifferentiated cells. High level expression of this protein is characteristic for early embryonic tissue and diverse tumors. HMGI-C can function as an architectural factor enhancing the activity of transcription factor NF-kappaB on the beta-interferon promoter. The protein has three minor groove DNA-binding domains (AT-hooks). Here, we describe the complex of HMGI-C with a fragment of the beta-interferon promoter. We show that the protein binds to NRDI and PRDII elements of the promoter with its first and second AT-hook, respectively. Phosphorylation by Cdc2 kinase leads to a partial derailing of the AT-hooks from the minor groove, affecting mainly the second binding domain. In contrast, binding to long AT stretches of DNA involves contacts with all three AT-hooks and is marginally sensitive to phosphorylation. Our data stress the importance of conformation of the DNA binding site and protein phosphorylation for its function.
ISSN:0021-9258
1083-351X