Docking-dependent Ubiquitination of the Interferon Regulatory Factor-1 Tumor Suppressor Protein by the

Characteristically for a regulatory protein, the IRF-1 tumorsuppressor turns over rapidly with a half-life of between20–40 min. This allows IRF-1 to reach new steady state pro-tein levels swiftly in response to changing environmental con-ditions. Whereas CHIP (C terminus of Hsc70-interactingprotein), appears to chaperone IRF-1 in unstressed cells, for-mation of a stable IRF-1CHIP complex is seen under specificstress conditions. Complex formation, in heat- or heavy metal-treated cells, is accompanied by a decrease in IRF-1 steadystate levels and an increase in IRF-1 ubiquitination. CHIPbinds directly to an intrinsically disordered domain in the cen-tral region of IRF-1 (residues 106–140), and this site is suffi-cient to form a stable complex with CHIP in cells and to com-pete in