Negative regulation of the RelA/p65 transactivation function by the product of the DEK proto-oncogene - PubMed (original) (raw)
. 2006 Sep 15;281(37):26802-12.
doi: 10.1074/jbc.M600915200. Epub 2006 Jul 7.
Affiliations
- PMID: 16829531
- DOI: 10.1074/jbc.M600915200
Free article
Negative regulation of the RelA/p65 transactivation function by the product of the DEK proto-oncogene
Morgan Sammons et al. J Biol Chem. 2006.
Free article
Abstract
NF-kappaB-mediated transcriptional activation is controlled at several levels including interaction with coregulatory proteins. To identify new proteins capable of modulating NF-kappaB-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-kappaB activity. DEK expression blocked p65-mediated activation of an NF-kappaB-dependent reporter gene and also inhibited TNFalpha-induced activation of the reporter gene. Chromatin Immunoprecipitation (ChIP) assays showed that DEK associates with the promoters of the NF-kappaB-regulated cIAP2 and IL-8 genes in untreated cells and dissociates from these promoters upon NF-kappaB binding in response to TNFalpha treatment. Moreover, the expression levels of an NF-kappaB-dependent reporter gene as well as the NF-kappaB-regulated Mcp-1 and IkappaBalpha 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.
Similar articles
- Silencing of the DEK gene induces apoptosis and senescence in CaSki cervical carcinoma cells via the up-regulation of NF-κB p65.
Liu K, Feng T, Liu J, Zhong M, Zhang S. Liu K, et al. Biosci Rep. 2012 Jun;32(3):323-32. doi: 10.1042/BSR20100141. Biosci Rep. 2012. PMID: 22390170 - The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression.
Ashburner BP, Westerheide SD, Baldwin AS Jr. Ashburner BP, et al. Mol Cell Biol. 2001 Oct;21(20):7065-77. doi: 10.1128/MCB.21.20.7065-7077.2001. Mol Cell Biol. 2001. PMID: 11564889 Free PMC article. - Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB.
Koyanagi M, Hijikata M, Watashi K, Masui O, Shimotohno K. Koyanagi M, et al. J Biol Chem. 2005 Apr 1;280(13):12430-7. doi: 10.1074/jbc.M410420200. Epub 2005 Jan 31. J Biol Chem. 2005. PMID: 15687488 - The Complexity of DEK Signaling in Cancer Progression.
Teng Y, Lang L, Jauregui CE. Teng Y, et al. Curr Cancer Drug Targets. 2018;18(3):256-265. doi: 10.2174/1568009617666170522094730. Curr Cancer Drug Targets. 2018. PMID: 28530531 Review. - Control of tumorigenesis and chemoresistance by the DEK oncogene.
Riveiro-Falkenbach E, Soengas MS. Riveiro-Falkenbach E, et al. Clin Cancer Res. 2010 Jun 1;16(11):2932-8. doi: 10.1158/1078-0432.CCR-09-2330. Epub 2010 May 25. Clin Cancer Res. 2010. PMID: 20501624 Free PMC article. Review.
Cited by
- The impact of the chromatin binding DEK protein in hematopoiesis and acute myeloid leukemia.
Wilcher KE, Page ERH, Privette Vinnedge LM. Wilcher KE, et al. Exp Hematol. 2023 Jul;123:18-27. doi: 10.1016/j.exphem.2023.05.002. Epub 2023 May 10. Exp Hematol. 2023. PMID: 37172756 Free PMC article. Review. - Long Non-Coding LEF1-AS1 Sponge miR-5100 Regulates Apoptosis and Autophagy in Gastric Cancer Cells via the miR-5100/DEK/AMPK-mTOR Axis.
Zhang H, Wang J, Wang Y, Li J, Zhao L, Zhang T, Liao X. Zhang H, et al. Int J Mol Sci. 2022 Apr 26;23(9):4787. doi: 10.3390/ijms23094787. Int J Mol Sci. 2022. PMID: 35563178 Free PMC article. - DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer.
Yang Y, Gao M, Lin Z, Chen L, Jin Y, Zhu G, Wang Y, Jin T. Yang Y, et al. Oncotarget. 2017 Oct 17;8(58):98708-98722. doi: 10.18632/oncotarget.21864. eCollection 2017 Nov 17. Oncotarget. 2017. PMID: 29228721 Free PMC article. - Stacking the DEK: from chromatin topology to cancer stem cells.
Privette Vinnedge LM, Kappes F, Nassar N, Wells SI. Privette Vinnedge LM, et al. Cell Cycle. 2013 Jan 1;12(1):51-66. doi: 10.4161/cc.23121. Epub 2012 Dec 19. Cell Cycle. 2013. PMID: 23255114 Free PMC article. Review. - Nuclear pore proteins and cancer.
Xu S, Powers MA. Xu S, et al. Semin Cell Dev Biol. 2009 Jul;20(5):620-30. doi: 10.1016/j.semcdb.2009.03.003. Epub 2009 Mar 18. Semin Cell Dev Biol. 2009. PMID: 19577736 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous