Ikappa b-alpha, the NF-kappa B inhibitory subunit, interacts with ANT, the mitochondrial ATP/ADP translocator.

The transcription factor NF-kappaB regulates a wide set of genes involved in the establishment of many cellular processes that control cell activation, proliferation, and apoptosis. IkappaB inhibitory subunits integrate NF-kappaB activation signals through phosphorylation and ubiquitination of its N-terminal domain. Using the two-hybrid system in yeast, we searched for IkappaB-alpha ...
N-terminal domain interactors and therefore potential NF-kappaB regulators. An interaction of IkappaB-alpha with the mitochondrial ATP/ADP translocator ANT was detected in yeast and confirmed in glutathione S-transferase pull-down assays and co-precipitation experiments in transfected cells. Subcellular cell fractionation, resistance to proteinase K treatment, and electron microscopy experiments demonstrated the presence of IkappaB-alpha and associated p65 NF-kappaB in the mitochondrial intermembrane space. IkappaB-alpha.NF-kappaB appeared to be released from mitochondria upon the induction of apoptosis by engagement of the Fas receptor. These data suggest that the mitochondrial IkappaB-alpha.NF-kappaB pool participates in the regulation of apoptosis.
Mesh Terms:
Apoptosis, Cell Line, Cloning, Molecular, DNA-Binding Proteins, Genes, Reporter, Glutathione Transferase, Human T-lymphotropic virus 1, Humans, I-kappa B Proteins, Intracellular Membranes, Jurkat Cells, Kinetics, Mitochondria, Mitochondrial ADP, ATP Translocases, NF-kappa B, Protein Subunits, Saccharomyces cerevisiae, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: Jun. 15, 2001
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