E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box

J Biol Chem. 1998 Dec 18;273(51):34302-9. doi: 10.1074/jbc.273.51.34302.

Abstract

Ubiquitin ligases are generally assumed to play a major role in substrate recognition and thus provide specificity to a particular ubiquitin modification system. The multicopy maintenance protein (Mcm) 7 subunit of the replication licensing factor-M was identified as a substrate of the E3-ubiquitin ligase/E6-AP by its interaction with human papillomavirus-18E6. Mcm7 is ubiquitinated in vivo in both an E6-AP-dependent and -independent manner. E6-AP functions in these reactions independently of the viral oncogene E6. We show that recognition of Mcm7 by E6-AP is mediated by a homotypic interaction motif present in both proteins, called the L2G box. These findings served as the basis for the definition of substrate specificity for E6-AP. A small cluster of proteins whose function is intimately associated with the control of cell growth and/or proliferation contains the L2G box and is thereby implicated in an E6-AP and, by default, HPV-E6-dependent ubiquitination pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies
  • Cell Cycle Proteins*
  • Conserved Sequence
  • DNA Primers
  • DNA Replication
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Ligases / chemistry
  • Ligases / metabolism*
  • Macromolecular Substances
  • Minichromosome Maintenance Complex Component 7
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Oligodeoxyribonucleotides
  • Papillomaviridae / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism*

Substances

  • Antibodies
  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • Ubiquitin-Protein Ligases
  • MCM7 protein, S cerevisiae
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 7
  • Ligases