Negative regulation of the RelA/p65 transactivation function by the product of the DEK proto-oncogene

作者：Sammons Morgan; Wan Shan Shan; Vogel Nancy L; Mientjes Edwin J; Grosveld Gerard; Ashburner Brian P^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281(37): 26802-26812.

DOI：10.1074/jbc.M600915200

NF-kappa B-mediated transcriptional activation is controlled at several levels including interaction with coregulatory proteins. To identify new proteins capable of modulating NF-kappa B-mediated activation, a cytoplasmic two-hybrid screen was performed using the p65 C-terminal transactivation domain as bait and identified the product of the DEK proto-oncogene. DEK is a ubiquitous nuclear protein that has been implicated in several types of cancer and autoimmune diseases. DEK appears to function in several nuclear processes including transcriptional repression and modulation of chromatin structure. Our data indicate that DEK functions as a transcriptional corepressor to repress NF-kappa B activity. DEK expression blocked p65-mediated activation of an NF-kappa B-dependent reporter gene and also inhibited TNF alpha-induced activation of the reporter gene. Chromatin Immunoprecipitation (ChIP) assays showed that DEK associates with the promoters of the NF-kappa B-regulated cIAP2 and IL-8 genes in untreated cells and dissociates from these promoters upon NF-kappa B-binding in response to TNF alpha treatment. Moreover, the expression levels of an NF-kappa B-dependent reporter gene as well as the NF-kappa B-regulated Mcp-1 and I kappa B alpha genes is increased in DEK-/- cells compared with wild-type cells. ChIP assays on these promoters show enhanced and prolonged binding of p65 and increased recruitment of the P/CAF coactivator. Overall, these data provide further evidence that DEK functions to negatively regulate transcription.

• 出版日期2006-9-15