Tumor necrosis factor alpha induction of NF-kappaB requires the novel coactivator SIMPL
| Autor: | Erin Haag Breese, Eva Vig-Varga, Younghee Lee, Mark G. Goebl, Hyung-Joo Kwon, Maureen A. Harrington, Yong Luo |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Transcriptional Activation
Proto-Oncogene Proteins c-jun Molecular Sequence Data Nuclear Localization Signals Gene Expression IκB kinase Biology Proinflammatory cytokine Cell Line chemistry.chemical_compound Transactivation Mice Gene expression Coactivator Animals Humans Amino Acid Sequence Molecular Biology Cell Nucleus Kinase Tumor Necrosis Factor-alpha Intracellular Signaling Peptides and Proteins NF-kappa B Transcription Factor RelA NF-κB Cell Biology NFKB1 Protein Structure Tertiary Protein Transport chemistry Receptors Tumor Necrosis Factor Type I Multiprotein Complexes Cancer research CCAAT-Enhancer-Binding Proteins Carrier Proteins |
| Zdroj: | Molecular and cellular biology. 24(21) |
| ISSN: | 0270-7306 |
| Popis: | A myriad of stimuli including proinflammatory cytokines, viruses, and chemical and mechanical insults activate a kinase complex composed of IkappaB kinase beta (IKK-beta), IKK-alpha, and IKK-gamma/N, leading to changes in NF-kappaB-dependent gene expression. However, it is not clear how the NF-kappaB response is tailored to specific cellular insults. Signaling molecule that interacts with mouse pelle-like kinase (SIMPL) is a signaling component required for tumor necrosis factor alpha (TNF-alpha)-dependent but not interleukin-1-dependent NF-kappaB activation. Herein we demonstrate that nuclear localization of SIMPL is required for type I TNF receptor-induced NF-kappaB activity. SIMPL interacts with nuclear p65 in a TNF-alpha-dependent manner to promote endogenous NF-kappaB-dependent gene expression. The interaction between SIMPL and p65 enhances p65 transactivation activity. These data support a model in which TNF-alpha activation of NF-kappaB dependent-gene expression requires nuclear relocalization of p65 as well as nuclear relocalization of SIMPL, generating a TNF-alpha-specific induction of gene expression. |
| Databáze: | OpenAIRE |
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