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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antibodies
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Cell Cycle Proteins*
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Conserved Sequence
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DNA Primers
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DNA Replication
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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HeLa Cells
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Humans
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Ligases / chemistry
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Ligases / metabolism*
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Macromolecular Substances
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Minichromosome Maintenance Complex Component 7
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Oligodeoxyribonucleotides
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Papillomaviridae / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Substrate Specificity
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism*
Substances
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Antibodies
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Cell Cycle Proteins
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DNA Primers
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DNA-Binding Proteins
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Macromolecular Substances
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Nuclear Proteins
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Oligodeoxyribonucleotides
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Peptide Fragments
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Ubiquitins
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Ubiquitin-Protein Ligases
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MCM7 protein, S cerevisiae
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MCM7 protein, human
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Minichromosome Maintenance Complex Component 7
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Ligases