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

Joohyun Ryu, Do Hee Lee

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume502
Issue number3
DOIs
StatePublished - Jul 20 2018

Keywords

  • Ataxin-1
  • Dual-specificity phosphatase 18
  • JNK
  • Polyglutamine
  • SUMO-1

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