• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


p57KIP2 modulates stress-activated signaling by inhibiting c-Jun NH2-terminal kinase/stress-activated protein Kinase.

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.

Pubmed ID: 12963725


  • Chang TS
  • Kim MJ
  • Ryoo K
  • Park J
  • Eom SJ
  • Shim J
  • Nakayama KI
  • Nakayama K
  • Tomita M
  • Takahashi K
  • Lee MJ
  • Choi EJ


The Journal of biological chemistry

Publication Data

November 28, 2003

Associated Grants


Mesh Terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p57
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases
  • Nuclear Proteins
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • Transfection
  • Ultraviolet Rays