Acetylation of importin-alpha nuclear import factors by CBP/p300

Curr Biol. 2000 Apr 20;10(8):467-70. doi: 10.1016/s0960-9822(00)00445-0.


Histone acetylases were originally identified because of their ability to acetylate histone substrates [1] [2] [3]. Acetylases can also target other proteins such as transcription factors [4] [5] [6] [7]. We asked whether the acetylase CREB-binding protein (CBP) could acetylate proteins not directly involved in transcription. A large panel of proteins, involved in a variety of cellular processes, were tested as substrates for recombinant CBP. This screen identified two proteins involved in nuclear import, Rch1 (human importin-alpha) and importin-alpha7, as targets for CBP. The acetylation site within Rch1 was mapped to a single residue, Lys22. By comparing the context of Lys22 with the sequences of other known substrates of CBP and the closely related acetylase p300, we identified G/SK (in the single-letter amino acid code) as a consensus acetylation motif. Mutagenesis of the glycine, as well as the lysine, severely impaired Rch1 acetylation, supporting the view that GK is part of a recognition motif for acetylation by CBP/p300. Using an antibody raised against an acetylated Rch1 peptide, we show that Rch1 was acetylated at Lys22 in vivo and that CBP or p300 could mediate this reaction. Lys22 lies within the binding site for a second nuclear import factor, importin-beta. Acetylation of Lys22 promoted interaction with importin-beta in vitro. Collectively, these results demonstrate that acetylation is not unique to proteins involved in transcription. Acetylation may regulate a variety of biological processes, including nuclear import.

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • CREB-Binding Protein
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Consensus Sequence
  • Glycine / chemistry
  • Glycine / genetics
  • Histone Acetyltransferases
  • Humans
  • Karyopherins
  • Lysine / chemistry
  • Lysine / genetics
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Sequence Alignment
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transformation, Genetic
  • alpha Karyopherins*
  • p300-CBP Transcription Factors


  • Carrier Proteins
  • Cell Cycle Proteins
  • Karyopherins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • alpha Karyopherins
  • karyopherin alpha 2
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lysine
  • Glycine