Phosphorylation of USP15 and USP4 Regulates Localization and Spliceosomal Deubiquitination

Tanuza Das, Eunice Eun Kyeong Kim, Eun Joo Song

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Deubiquitinating enzymes have key roles in diverse cellular processes whose enzymatic activities are regulated by different mechanisms including post-translational modification. Here, we show that USP15 is phosphorylated, and its localization and activity are dependent on the phosphorylation status. Nuclear-cytoplasmic fractionation and mass spectrometric analysis revealed that Thr149 and Thr219 of human USP15, which is conserved among different species, are phosphorylated in the cytoplasm. The phosphorylation status of USP15 at these two positions alters the interaction with its partner protein SART3, consequently leading to its nuclear localization and deubiquitinating activity toward the substrate PRP31. Treatment of cells with purvalanol A, a cyclin-dependent kinase inhibitor, results in nuclear translocation of USP15. USP4, another deubiquitinating enzyme with a high sequence homology and domain structure as USP15, also showed purvalanol A-dependent changes in activity and localization. Collectively, our data suggest that modifications of USP15 and USP4 by phosphorylation are important for the regulation of their localization required for cellular function in the spliceosome.

Original languageEnglish
Pages (from-to)3900-3912
Number of pages13
JournalJournal of Molecular Biology
Volume431
Issue number19
DOIs
StatePublished - 6 Sep 2019

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Science and ICT (2017R1A2B3007224 and 2019R1A2C2004052) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of the Republic of Korea (CAP-16-03-KRIBB). Dr. Tanuza Das was supported by Korea Research Fellowship program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (2017HID3A1A02054608). Declaration of Competing Interest: The authors declare no conflict of interest.

Funding Information:
This work was supported by a National Research Foundation of Korea grant funded by the Ministry of Science and ICT (2017R1A2B3007224 and 2019R1A2C2004052) and the R&D Convergence Program of NST ( National Research Council of Science & Technology ) of the Republic of Korea (CAP-16-03-KRIBB). Dr. Tanuza Das was supported by Korea Research Fellowship program through the National Research Foundation of Korea funded by the Ministry of Science and ICT ( 2017HID3A1A02054608 ).

Publisher Copyright:
© 2019

Keywords

  • localization
  • phosphorylation
  • SART3
  • USP15

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