TY - JOUR
T1 - Phosphorylation of USP15 and USP4 Regulates Localization and Spliceosomal Deubiquitination
AU - Das, Tanuza
AU - Kim, Eunice Eun Kyeong
AU - Song, Eun Joo
N1 - 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
PY - 2019/9/6
Y1 - 2019/9/6
N2 - 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.
AB - 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.
KW - localization
KW - phosphorylation
KW - SART3
KW - USP15
UR - http://www.scopus.com/inward/record.url?scp=85070080179&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2019.07.023
DO - 10.1016/j.jmb.2019.07.023
M3 - Article
C2 - 31330151
AN - SCOPUS:85070080179
SN - 0022-2836
VL - 431
SP - 3900
EP - 3912
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 19
ER -