p57KIP2 Modulates Stress-activated Signaling by Inhibiting c-Jun NH2-terminal Kinase/Stress-activated Protein Kinase

Tong Shin Chang, Myung Jin Kim, Kanghyun Ryoo, Jihyun Park, Soo Jung Eom, Jaekyung Shim, Keiichi I. Nakayama, Keiko Nakayama, Motowo Tomita, Katsuhiko Takahashi, Min Jae Lee, Eui Ju Choi

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53 Citations (Scopus)

Abstract

p57KIP2, a member of the Cip/Kip family of enzymes that inhibit several cyclin-dependent kinases, plays a role in many biological events including cell proliferation, differentiation, apoptosis, tumorigenesis and developmental changes. The human p57KIP2 gene is located in chromosome 11p15.5, a region implicated in sporadic cancers and Beckwith-Wiedemann syndrome. We here report that p57KIP2 physically interacts with and inhibits c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK). The carboxyl-terminal QT domain of p57KIP2 is crucial for the inhibition of JNK/SAPK. Overexpressed p57KIP2 also suppressed UV- and MEKK1-induced apoptotic cell death. p57KIP2 expression during C2C12 myoblast differentiation resulted in repression of the JNK activity stimulated by UV light. Furthermore, UV-stimulated JNK1 activity was higher in mouse embryonic fibroblasts derived from p57-/- mice than in the cells from wild-type mice. Taken together, these findings suggest that p57KIP2 modulates stress-activated signaling by functioning as an endogenous inhibitor of JNK/SAPK.

Original languageEnglish
Pages (from-to)48092-48098
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number48
DOIs
Publication statusPublished - 2003 Nov 28

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chang, T. S., Kim, M. J., Ryoo, K., Park, J., Eom, S. J., Shim, J., Nakayama, K. I., Nakayama, K., Tomita, M., Takahashi, K., Lee, M. J., & Choi, E. J. (2003). p57KIP2 Modulates Stress-activated Signaling by Inhibiting c-Jun NH2-terminal Kinase/Stress-activated Protein Kinase. Journal of Biological Chemistry, 278(48), 48092-48098. https://doi.org/10.1074/jbc.M309421200