Functionally distinct monomers and trimers produced by a viral oncoprotein

Oncogene. 2008 Feb 28;27(10):1412-20. doi: 10.1038/sj.onc.1210784. Epub 2007 Sep 10.


While the process of homo-oligomer formation and disassembly into subunits represents a common strategy to regulate protein activity, reports of proteins in which the subunit and homo-oligomer perform independent functions are scarce. Tumorigenesis induced by the adenovirus E4-ORF1 oncoprotein depends on its binding to a select group of cellular PDZ proteins, including MUPP1, MAGI-1, ZO-2 and Dlg1. We report here that in cells E4-ORF1 exists as both a monomer and trimer and that monomers specifically bind and sequester MUPP1, MAGI-1 and ZO-2 within insoluble complexes whereas trimers specifically bind Dlg1 and promote its translocation to the plasma membrane. This work exposes a novel strategy wherein the oligomerization state of a protein not only determines the capacity to bind separate related targets but also couples the interactions to different functional consequences.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenovirus E4 Proteins / chemistry*
  • Adenovirus E4 Proteins / genetics
  • Adenovirus E4 Proteins / metabolism*
  • Adenoviruses, Human / chemistry*
  • Adenoviruses, Human / enzymology
  • Adenoviruses, Human / genetics
  • Amino Acid Sequence
  • Animals
  • Humans
  • Molecular Sequence Data
  • Protein Binding / physiology
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary / physiology
  • Pyrophosphatases / chemistry
  • Pyrophosphatases / genetics


  • Adenovirus E4 Proteins
  • Pyrophosphatases
  • dUTP pyrophosphatase