Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein.
Defining the molecular mechanisms that integrate diverse signaling pathways at the level of gene transcription remains a central issue in biology. Here, we demonstrate that interleukin-1beta (IL-1beta) causes nuclear export of a specific N-CoR corepressor complex, resulting in derepression of a specific subset of NF-kappaB-regulated genes, exemplified by the tetraspanin KAI1 that regulates membrane receptor function. Nuclear export of the N-CoR/TAB2/HDAC3 complex by IL-1beta is temporally linked to selective recruitment of a Tip60 coactivator complex. Surprisingly, KAI1 is also directly activated by a ternary complex, dependent on the acetyltransferase activity of Tip60, consisting of the presenilin-dependent C-terminal cleavage product of the amyloid beta precursor protein (APP), Fe65, and Tip60, identifying a specific in vivo gene target of an APP-dependent transcription complex in the brain.
Pubmed ID: 12150997 RIS Download
Acetyltransferases | Active Transport, Cell Nucleus | Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Amyloid beta-Protein Precursor | Animals | Antigens, CD | Antigens, CD82 | Carrier Proteins | Cells, Cultured | Cercopithecus aethiops | Histone Acetyltransferases | Humans | Interleukin-1 | MAP Kinase Kinase Kinase 1 | Membrane Glycoproteins | Molecular Sequence Data | NF-kappa B | Nerve Tissue Proteins | Nuclear Proteins | Nuclear Receptor Co-Repressor 1 | Promoter Regions, Genetic | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | RNA, Messenger | Repressor Proteins | Signal Transduction | Up-Regulation