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.
Mesh Terms:
Acetyltransferases, Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Amyloid beta-Protein Precursor, Animals, Antigens, CD, Carrier Proteins, Cells, Cultured, Cercopithecus aethiops, Histone Acetyltransferases, Humans, Interleukin-1, Kangai-1 Protein, 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
Cell
Date: Jul. 12, 2002
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