Copine-I represses NF-κB transcription by endoproteolysis of p65
| Autor: | Catherine S. Ramsey, Marty W. Mayo, P B Stoddard, Duo Li, C E Creutz, Fan Yeung |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research Transcription Genetic Response element E-box Transcription coregulator Biology Models Biological Cell Line Sp3 transcription factor Cell Line Tumor Genetics Humans RNA Small Interfering Molecular Biology Phospholipids Sp1 transcription factor General transcription factor NF-kappa B Prostatic Neoplasms Promoter DNA Molecular biology Protein Structure Tertiary Cell biology Gene Expression Regulation Synaptotagmin I TAF2 Carrier Proteins |
| Zdroj: | Oncogene. 27:3516-3526 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1211030 |
| Popis: | Nuclear factor-kappaB (NF-kappaB) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. Identifying regulators that control the half-life of NF-kappaB is important to understanding molecular processes that control the duration of transcriptional responses. In this study we identify copine-I, a calcium phospholipid-binding protein, as a novel repressor that physically interacts with p65 to inhibit NF-kappaB transcription. Knockdown of copine-I by siRNA increases tumor necrosis factor alpha-stimulated NF-kappaB transcription, while copine-I expression blocks endogenous transcription. Copine-I abolishes NF-kappaB transcription by inducing endoprotease processing of the N-terminus of p65, a process antagonized by IkappaB alpha. Copine-I stimulates endoproteolysis of p65 within a conserved region that is required for base-specific contact with DNA. p65 proteins lacking the N-terminus fail to bind to DNA and act as dominant-negative molecules that inhibit NF-kappaB transcription. Our work provides evidence that copine-I regulates the half-life of NF-kappaB transcriptional responses through a novel mechanism that involves endoproteolysis of the p65 protein. |
| Databáze: | OpenAIRE |
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