GSBS Student Publications


c-Jun NH(2)-terminal kinase is essential for the regulation of AP-1 by tumor necrosis factor

UMMS Affiliation

Graduate School of Biomedical Sciences; Howard Hughes Medical Institute and Program in Molecular Medicine



Document Type


Medical Subject Headings

Activating Transcription Factor 2; Animals; Cells, Cultured; Cyclic AMP Response Element-Binding Protein; Enzyme Activation; Gene Expression; Inflammation Mediators; Interferon Type II; Interleukin-6; MAP Kinase Signaling System; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Mitogen-Activated Protein Kinases; Phosphorylation; Recombinant Proteins; Transcription Factor AP-1; Transcription Factors; Tumor Necrosis Factor-alpha


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.

Rights and Permissions

Citation: Mol Cell Biol. 2003 Apr;23(8):2871-82.

Related Resources

Link to Article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID