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Schaefer JB and Morgan DO  (2011) Protein-linked ubiquitin chain structure restricts activity of deubiquitinating enzymes. J Biol Chem 286(52):45186-96

Abstract: The attachment of lysine 48 (Lys(48))-linked polyubiquitin chains to proteins is a universal signal for degradation by the proteasome. Here, we report that long Lys(48)-linked chains are resistant to many deubiquitinating enzymes (DUBs). Representative enzymes from this group, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrates but are slow to remove longer Lys(48)-linked chains. This resistance is lost if the structure of Lys(48)-linked chains is disrupted by mutation of ubiquitin or if chains are linked through Lys(63). In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, regardless of chain structure. We propose that the resistance to many DUBs of long, substrate-attached Lys(48)-linked chains helps ensure that proteins are maintained free from ubiquitin until a threshold of ubiquitin ligase activity enables degradation.

Status: Published Type: Journal Article PubMed ID: 22072716

Topics addressed in this paper

Number of different genes curated to this paper: 21

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Topics Genes linked to topics (#1 - 10 )
DOA4 OTU1 OTU2 PDS1 RPN11 UBP1 UBP10 UBP11 UBP12 UBP13
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Topics Genes linked to topics (#11 - 20 )
UBP14 UBP15 UBP16 UBP2 UBP3 UBP5 UBP6 UBP7 UBP8 UBP9
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Topics Genes linked to topics (#21 )
YUH1
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