2020
DOI: 10.1042/bcj20200536
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Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation

Abstract: Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL domains of USP19 and structural insights into their domain interactions. We found that the tandem CS domains fold … Show more

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Cited by 5 publications
(4 citation statements)
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“…Several USPs are reported to be regulated by the intrinsic regions that physically interact with their catalytic domains [26,28,[40][41][42]. Among these, USP25 had previously been the only USP for which the activity was inhibited on a well-defined structural basis.…”
Section: Discussionmentioning
confidence: 99%
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“…Several USPs are reported to be regulated by the intrinsic regions that physically interact with their catalytic domains [26,28,[40][41][42]. Among these, USP25 had previously been the only USP for which the activity was inhibited on a well-defined structural basis.…”
Section: Discussionmentioning
confidence: 99%
“…Some USPs are activated by specific interacting proteins that bind to catalytic USP domains [2125] or other domains [2628]. USP8, which has a phosphorylation-dependent 14-3-3 binding motif (Fig.…”
mentioning
confidence: 99%
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“…This family is characterized by the presence of a highly conserved USP catalytic domain fold ( Hu et al, 2002 ; Hu et al, 2005 ; Avvakumov et al, 2006 ; Renatus et al, 2006 ; Komander et al, 2008 ), which holds two well-conserved motifs (Cys and His boxes), each containing the critical residues for the enzymatic activity. Moreover, USP19 contains two CHORD-SGT1/P23 domains (namely CS1 and CS2) at its N-terminus, which are relevant for the interaction with other proteins, as well as for the intra-molecular inhibition and regulation of the catalytic core ( Xue et al, 2020 ) ( Figure 2 ).…”
Section: General Properties Of Usp19mentioning
confidence: 99%