Dual-specificity phosphatase 18 modulates the SUMOylation and aggregation of Ataxin-1.

We previously reported that SUMOylation promotes the aggregation of ataxin-1 and JNK is involved in the process. Here we show that dual-specificity phosphatase 18 (DUSP18), a member of protein tyrosine phosphatases, exerts the opposite effects on ataxin-1. DUSP18 associated with ataxin-1 and suppressed JNK activated by ataxin-1. Interestingly DUSP18, but ...
not the other DUSPs interacting with ataxin-1, caused the mobility shift of ataxin-1. De-phosphorylation by DUSP18 was initially suspected as a cause for such an effect; however, the phosphorylation of ataxin-1 was unchanged. Instead DUSP18 inhibited SUMOylation and reduced ataxin-1 aggregation. The catalytic mutant of DUSP18 failed to reduce the SUMOylation and aggregation of ataxin-1 indicating that the phosphatase activity is indispensable for the effects. Moreover, DUSP18 disrupted the co-localization of ataxin-1 with the PML component Sp100. These results together implicate that JNK and DUSP18 reciprocally modulate the SUMOylation, which plays a regulatory role in the aggregation of ataxin-1.
Mesh Terms:
Antigens, Nuclear, Ataxin-1, Autoantigens, Catalytic Domain, Dual-Specificity Phosphatases, HEK293 Cells, Humans, MAP Kinase Signaling System, Mutant Proteins, Peptides, Phosphorylation, Protein Aggregates, Protein Aggregation, Pathological, Sumoylation
Biochem. Biophys. Res. Commun.
Date: Dec. 20, 2017
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