P38 stabilizes Snail by suppressing DyRK2-mediated phosphorylation that is required for GSK3b-BTRCP–induced snail degradation

Ki Jun Ryu, Sun Mi Park, Seung Ho Park, In Kyu Kim, Hyeontak Han, Hyo Jin Kim, Seon Hee Kim, Keun Seok Hong, Hyemin Kim, Minju Kim, Sung Jin Yoon, Killivalavan Asaithambi, Kon Ho Lee, Jae Yong Park, Young Sool Hah, Hee Jun Cho, Jong In Yook, Jung Wook Yang, Gyung Hyuck Ko, Gyemin LeeYang Jae Kang, Cheol Hwangbo, Kwang Dong Kim, Young Jun Park, Jiyun Yoo

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Snail is a key regulator of epithelial–mesenchymal tran-tively suppressed DYRK2-mediated Ser104 phosphoryla-sition (EMT), which is a major step in tumor metastasis. tion, which is critical for GSK3b-dependent Snail phosphor-Although the induction of Snail transcription precedes EMT, ylation and bTrCP-mediated Snail ubiquitination and deg-posttranslational regulation, especially phosphorylation of radation. Importantly, functional studies and analysis of Snail, is critical for determining Snail protein levels or clinical samples established a crucial role for the p38–Snail stability, subcellular localization, and the ability to induce axis in regulating ovarian cancer EMT and metastasis. These EMT. To date, several kinases are known that enhance the results indicate the potential therapeutic value of targeting stability of Snail by preventing its ubiquitination; however, the p38–Snail axis in ovarian cancer. the molecular mechanism(s) underlying this are still unclear. Here, we identified p38 MAPK as a crucial post-Significance: These findings identify p38 MAPK as a novel translational regulator that enhances the stability of Snail. regulator of Snail protein stability and potential therapeutic p38 directly phosphorylated Snail at Ser107, and this effec-target in ovarian cancer.

Original languageEnglish
Pages (from-to)4135-4148
Number of pages14
JournalCancer Research
Issue number16
Publication statusPublished - 2019 Aug 15

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Education (NRF-2013R1A1A2057753 to J. Yoo), the Korea government (MSIP; NRF-2017R1A2B4003185 to J. Yoo and NRF-2018M3A9H3023077 to Y.-J. Park), and grants from the KRIBB Research Initiative Program, Republic of Korea.

Publisher Copyright:
©2019 American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'P38 stabilizes Snail by suppressing DyRK2-mediated phosphorylation that is required for GSK3b-BTRCP–induced snail degradation'. Together they form a unique fingerprint.

Cite this