Acetylation of the adenovirus-transforming protein E1A determines nuclear localization by disrupting association with importin-α

Dana L. Madison, Peter Yaciuk, Roland P.S. Kwok, James R. Lundblad

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Posttranslational modifications may alter the biochemical functions of a protein by modifying associations with other macromolecules, allosterically altering intrinsic catalytic activities, or determining subcellular localization. The adenovirus-transforming protein E1A is acetylated by its cellular targets, the co-activators CREB-binding protein, p300, and p300/CREB-binding protein-associated factor in vitro and also in vivo at a single lysine residue (Lys239) within a multifunctional carboxyl-terminal domain necessary for both nuclear localization and interaction with the transcriptional corepressor carboxyl-terminal binding protein (CtBP). In contrast to a previous report, we demonstrate that acetylation of Lys239 does not disrupt CtBP binding and that 12 S E1A-mediated repression of CREB-binding protein-dependent transcription does not require recruitment of CtBP. Instead we find that the cytoplasmic fraction of E1-transformed 293 cells is enriched for acetylated E1A with relative exclusion from the nuclear compartment. Whereas wild type 12 S E1A binds importin-α3, binding affinity was markedly reduced both by single amino acid substitution mutations and acetylation at Lys239. This is the first demonstration that acetylation may alter nuclear partitioning by direct interference with nuclear import receptor recognition. The finding that the cytoplasmic fraction of E1A is acetylated indicates that EIA may exert its pleiotropic effects on cellular transformation in part by affecting cytoplasmic processes.

Original languageEnglish (US)
Pages (from-to)38755-38763
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number41
DOIs
StatePublished - Oct 11 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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