JNK2: A Negative Regulator of Cellular Proliferation

Cell Cycle. 2004 Dec;3(12):1520-3. doi: 10.4161/cc.3.12.1315. Epub 2004 Dec 18.


The three different c-Jun N-terminal kinases (JNKs) are activated in multiple cell types by both apoptotic and mitogenic signals, and in turn regulate the activity of transcription factors such as c-Jun. Being highly homologous and ubiquitously expressed, the JNK1 and JNK2 proteins have been thought to perform redundant functions in many physiological process. However, our data from Jnk1-/- or Jnk2-/- cells and mice suggest that both JNK isozymes perform distinct functions in regulating cellular proliferation via differential regulation of c-Jun, which is a critical regulator of cell-cycle progression. Absence of JNK1, the positive regulator of c-Jun, leads to decreased fibroblast proliferation. In contrast, JNK2 deficiency leads to reduced c-Jun degradation, thereby augmenting c-Jun levels and cellular proliferation. Various cell types including fibroblasts, erythroblasts and hepatocytes from Jnk2-/- mice exhibit increased proliferation rates compared to their wild-type counterparts. These data therefore suggests that JNK2, in contrast to JNK1, is a negative regulator of cellular proliferation in multiple cell types.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation*
  • Gene Expression Regulation
  • Hepatocytes / pathology
  • Keratinocytes
  • Mitogen-Activated Protein Kinase 9 / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism


  • Proto-Oncogene Proteins c-jun
  • Mitogen-Activated Protein Kinase 9