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ATXN3 deubiquitinates STUB1. 20 / 20
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"Upon completion of substrate ubiquitination, ataxin-3 deubiquitinates CHIP, effectively terminating the reaction."

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"We next tested whether the presence of UbcH5c, which is needed to polyubiquitinate HSP90, reduced the amount of ataxin-3 needed to deubiquitinate Ub-CHIP in active ubiquitination assays."

"Indeed, ataxin-3 not only deubiquitinated CHIP, but also trimmed Ub conjugates on CHIP substrates, thereby regulating the length of Ub chains."

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"Intriguingly, deubiquitination of Ub-CHIP by ataxin-3 correlated temporally with the accumulation of ubiquitinated substrates and occurred whether ataxin-3 had a normal or expanded polyglutamine domain (XREF_FIG)."

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"Upon completion of substrate ubiquitination, as determined by chain length, ataxin-3 presumably binds ubiquitinated substrate through its UIMs and deubiquitinates CHIP, thus terminating the reaction (XREF_FIG) [XREF_BIBR]."

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"Importantly, ataxin-3 deubiquitinates CHIP, terminating CHIP-substrate interaction; polyQ expansion of ataxin-3 increases its affinity for CHIP and decreases CHIP levels in SCA3 mice, suggesting a surprising role for coordinated regulation of CHIP and ataxin-3 as well as dysregulation of this process in SCA3."

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"Evidence further supporting this notion that the ability of ataxin-3 to deubiquitinate CHIP is coupled to the ligase activity of CHIP, came from assays in which ataxin-3-mediated deubiquitination of CHIP did not occur until after poly-Ub conjugates on substrate proteins had attained a certain length."

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"The above results do not exclude the possibility that ubiquitin chains per se rather than polyubiquitinated substrates facilitate deubiquitination of CHIP by ataxin-3."

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"To determine whether deubiquitination of Ub-CHIP by ataxin-3 requires the presence of ubiquitinated substrate, we performed CHIP ubiquitination reactions with increasing concentrations of HSP90 as substrate, in the presence or absence of ataxin-3 and the chain elongating E2, UbcH5c (XREF_FIG), then assessed the ubiquitin state of CHIP at the end of the reaction."

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"Intriguingly, monoubiquitination of CHIP appears to enhance the interaction between ataxin-3 and CHIP, and when bound, ataxin-3 can now deubiquitinate CHIP."

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"Once this occurred, ataxin-3 could now deubiquitinate both CHIP and its substrates, trimming the Ub conjugates at the distal ends."

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"Ataxin-3 deubiquitinates CHIP upon completion of substrate polyubiquitination."

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"In response to substrate polyubiquitination, ataxin-3 deubiquitinates CHIP."

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"As expected, the presence of this chain elongating E2 markedly enhanced deubiquitination of CHIP by ataxin-3 (XREF_FIG)."

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"The fact that efficient deubiquitination of Ub-CHIP by ataxin-3 requires the presence of polyubiquitinated substrate suggests that the UIMs of ataxin-3 play an essential role in this process."

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"In reactions containing ataxin-3 and Ube2w but not UbcH5c (thus preventing chain extension), ataxin-3 did not deubiquitinate Ub-CHIP (XREF_FIG)."

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"Ataxin-3 presumably binds polyubiquitinated substrates through its ubiquitin interacting domain and deubiquitinates CHIP to terminate the reaction."

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"Once the substrates have been polyubiquitinated, Ataxin-3 deubiquitinates Ub-CHIP, leading to the termination of CHIP mediated substrate ubiquitination."

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"Here we observed that deubiquitination of CHIP by ataxin-3 occurs in response to the completion of substrate ubiquitination."

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"Deubiquitination of CHIP by ataxin-3 was found to be only active if the poly-ubiquitin chain on target substrates reaches a critical length, preventing extra ubiquitin incorporation [XREF_BIBR]."