c-Jun NH(2)-terminal kinase is essential for the regulation of AP-1 by tumor necrosis factor
Graduate School of Biomedical Sciences; Howard Hughes Medical Institute and Program in Molecular Medicine
Life Sciences | Medicine and Health Sciences
The c-Jun NH(2)-terminal kinase (JNK) is activated by the cytokine tumor necrosis factor (TNF). This pathway is implicated in the regulation of AP-1-dependent gene expression by TNF. To examine the role of the JNK signaling pathway, we compared the effects of TNF on wild-type and Jnk1(-/-) Jnk2(-/-) murine embryo fibroblasts. We show that JNK is required for the normal regulation of AP-1 by TNF. The JNK-deficient cells exhibited decreased expression of c-Jun, JunD, c-Fos, Fra1, and Fra2; decreased phosphorylation of c-Jun and JunD; and decreased AP-1 DNA binding activity. The JNK-deficient cells also exhibited defects in the regulation of the AP-1-related transcription factor ATF2. These changes were associated with marked defects in TNF-regulated gene expression. The JNK signal transduction pathway is therefore essential for AP-1 transcription factor regulation in cells exposed to TNF.
DOI of Published Version
Mol Cell Biol. 2003 Apr;23(8):2871-82.
Molecular and cellular biology
Ventura J, Kennedy NJ, Lamb JA, Flavell RA, Davis RJ. (2003). c-Jun NH(2)-terminal kinase is essential for the regulation of AP-1 by tumor necrosis factor. GSBS Student Publications. https://doi.org/10.1128/MCB.23.8.2871-2882.2003. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1310