Docking-dependent ubiquitination of the interferon regulatory factor-1 tumor suppressor protein by the ubiquitin ligase CHIP.

Characteristically for a regulatory protein, the IRF-1 tumor suppressor turns over rapidly with a half-life of between 20-40 min. This allows IRF-1 to reach new steady state protein levels swiftly in response to changing environmental conditions. Whereas CHIP (C terminus of Hsc70-interacting protein), appears to chaperone IRF-1 in unstressed cells, ...
formation of a stable IRF-1·CHIP complex is seen under specific stress conditions. Complex formation, in heat- or heavy metal-treated cells, is accompanied by a decrease in IRF-1 steady state levels and an increase in IRF-1 ubiquitination. CHIP binds directly to an intrinsically disordered domain in the central region of IRF-1 (residues 106-140), and this site is sufficient to form a stable complex with CHIP in cells and to compete in trans with full-length IRF-1, leading to a reduction in its ubiquitination. The study reveals a complex relationship between CHIP and IRF-1 and highlights the role that direct binding or "docking" of CHIP to its substrate(s) can play in its mechanism of action as an E3 ligase.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Cell Line, Tumor, HSP70 Heat-Shock Proteins, Heat-Shock Response, Humans, Interferon Regulatory Factor-1, Metals, Heavy, Molecular Sequence Data, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Tumor Suppressor Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
J. Biol. Chem.
Date: Jan. 07, 2011
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