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 journalArticle

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Abstract

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
Volume79
Issue number16
DOIs
Publication statusPublished - 2019 Aug 15

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Snails
Phosphorylation
Ovarian Neoplasms
Ubiquitination
p38 Mitogen-Activated Protein Kinases
Neoplasm Metastasis
Protein Stability
Phosphotransferases
Therapeutics
Neoplasms
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

P38 stabilizes Snail by suppressing DyRK2-mediated phosphorylation that is required for GSK3b-BTRCP–induced snail degradation. / Ryu, Ki Jun; Park, Sun Mi; Park, Seung Ho; Kim, In Kyu; Han, Hyeontak; Kim, Hyo Jin; Kim, Seon Hee; Hong, Keun Seok; Kim, Hyemin; Kim, Minju; Yoon, Sung Jin; Asaithambi, Killivalavan; Lee, Kon Ho; Park, Jae-Yong; Hah, Young Sool; Cho, Hee Jun; Yook, Jong In; Yang, Jung Wook; Ko, Gyung Hyuck; Lee, Gyemin; Kang, Yang Jae; Hwangbo, Cheol; Kim, Kwang Dong; Park, Young Jun; Yoo, Jiyun.

In: Cancer Research, Vol. 79, No. 16, 15.08.2019, p. 4135-4148.

Research output: Contribution to journalArticle

Ryu, KJ, Park, SM, Park, SH, Kim, IK, Han, H, Kim, HJ, Kim, SH, Hong, KS, Kim, H, Kim, M, Yoon, SJ, Asaithambi, K, Lee, KH, Park, J-Y, Hah, YS, Cho, HJ, Yook, JI, Yang, JW, Ko, GH, Lee, G, Kang, YJ, Hwangbo, C, Kim, KD, Park, YJ & Yoo, J 2019, 'P38 stabilizes Snail by suppressing DyRK2-mediated phosphorylation that is required for GSK3b-BTRCP–induced snail degradation', Cancer Research, vol. 79, no. 16, pp. 4135-4148. https://doi.org/10.1158/0008-5472.CAN-19-0049
Ryu, Ki Jun ; Park, Sun Mi ; Park, Seung Ho ; Kim, In Kyu ; Han, Hyeontak ; Kim, Hyo Jin ; Kim, Seon Hee ; Hong, Keun Seok ; Kim, Hyemin ; Kim, Minju ; Yoon, Sung Jin ; Asaithambi, Killivalavan ; Lee, Kon Ho ; Park, Jae-Yong ; Hah, Young Sool ; Cho, Hee Jun ; Yook, Jong In ; Yang, Jung Wook ; Ko, Gyung Hyuck ; Lee, Gyemin ; Kang, Yang Jae ; Hwangbo, Cheol ; Kim, Kwang Dong ; Park, Young Jun ; Yoo, Jiyun. / P38 stabilizes Snail by suppressing DyRK2-mediated phosphorylation that is required for GSK3b-BTRCP–induced snail degradation. In: Cancer Research. 2019 ; Vol. 79, No. 16. pp. 4135-4148.
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abstract = "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.",
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AU - Kim, In Kyu

AU - Han, Hyeontak

AU - Kim, Hyo Jin

AU - Kim, Seon Hee

AU - Hong, Keun Seok

AU - Kim, Hyemin

AU - Kim, Minju

AU - Yoon, Sung Jin

AU - Asaithambi, Killivalavan

AU - Lee, Kon Ho

AU - Park, Jae-Yong

AU - Hah, Young Sool

AU - Cho, Hee Jun

AU - Yook, Jong In

AU - Yang, Jung Wook

AU - Ko, Gyung Hyuck

AU - Lee, Gyemin

AU - Kang, Yang Jae

AU - Hwangbo, Cheol

AU - Kim, Kwang Dong

AU - Park, Young Jun

AU - Yoo, Jiyun

PY - 2019/8/15

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