Nuclear import of the histone acetyltransferase complex SAS-I in Saccharomyces cerevisiae

J Cell Sci. 2005 Apr 1;118(Pt 7):1473-84. doi: 10.1242/jcs.01739.

Abstract

The protein complex SAS-I links histone acetylation to the assembly of repressed chromatin in Saccharomyces cerevisiae. Sas2p, the histone acetyltransferase subunit of SAS-I, forms a complex with Sas4p and Sas5p, which are both required for maximal complex activity. In this study, we found that Sas4p was the central subunit of the SAS-I complex, bridging Sas2p and Sas5p. We demonstrated that the nuclear import of Sas2p and Sas5p was mediated by two karyopherins/importins, Kap123p and Pse1p, and both were associated in vivo with these importins. By contrast, Sas4p was not a substrate of Kap123p or Pse1p, suggesting that the nuclear import of the SAS-I subunits occurred independently of each other. Several other non-essential karyopherins were not involved in the nuclear import of SAS-I subunits. When the putative nuclear localization signal (NLS) of Sas2p was deleted, nuclear accumulation of Sas2p was significantly decreased. By contrast, deletion of the proposed NLS of Sas4p had no influence on its nuclear localization. An unknown signal region was located in the N-terminal domain of Sas5p and was responsible for the nuclear import by Kap123p and Pse1p. We found a striking similarity between the NLS sequences of Sas2p and those of histones H3 and H4, which were recently reported to be further import substrates of Kap123p and Pse1p. A database search based on the aligned consensus sequence revealed potential new import substrates of the Kap123p and Pse1p nuclear import pathways, which are connected to chromatin function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / chemistry
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Active Transport, Cell Nucleus / physiology
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Histone Acetyltransferases
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Multienzyme Complexes / metabolism*
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology
  • beta Karyopherins

Substances

  • Carrier Proteins
  • Kap123 protein, S cerevisiae
  • Membrane Transport Proteins
  • Multienzyme Complexes
  • PSE1 protein, S cerevisiae
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • beta Karyopherins
  • Green Fluorescent Proteins
  • Acetyltransferases
  • Sas4 protein, S cerevisiae
  • Sas5 protein, S cerevisiae
  • Histone Acetyltransferases
  • Sas2 protein, S cerevisiae