Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein

Cell. 2002 Jul 12;110(1):55-67. doi: 10.1016/s0092-8674(02)00809-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / physiology
  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloid beta-Protein Precursor / physiology*
  • Animals
  • Antigens, CD*
  • Carrier Proteins / physiology
  • Cells, Cultured
  • Chlorocebus aethiops
  • Histone Acetyltransferases
  • Humans
  • Interleukin-1 / physiology*
  • Kangai-1 Protein
  • Lysine Acetyltransferase 5
  • MAP Kinase Kinase Kinase 1*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Nuclear Receptor Co-Repressor 1
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins*
  • RNA, Messenger / biosynthesis
  • Repressor Proteins / physiology*
  • Signal Transduction
  • Up-Regulation

Substances

  • APBB1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Amyloid beta-Protein Precursor
  • Antigens, CD
  • CD82 protein, human
  • Carrier Proteins
  • Interleukin-1
  • Kangai-1 Protein
  • Membrane Glycoproteins
  • NCOR1 protein, human
  • NF-kappa B
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Repressor Proteins
  • TAB2 protein, human
  • Acetyltransferases
  • Histone Acetyltransferases
  • KAT5 protein, human
  • Lysine Acetyltransferase 5
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human