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However, accumulating evidence indicated that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cell lines, express immunoglobulins. The mechanisms underlying the expression of Igs in nonlymphoid cells remain unknown. On the basis of our previous finding that expression of kappa light chain in NPC cells can be upregulated by EBV-encoded latent membrane protein 1(LMP1) through the activation of NF-\u03baB and AP-1 signaling pathways, we thus use NPC cells as model to further explore the molecular mechanisms of nonlymphoid cells expressing Ig kappa.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this study, luciferase reporter plasmid containing human wild-type iE<jats:sub>\u03ba<\/jats:sub>, and its derivative plasmids containing mutant binding sites for transcription factor NF-\u03baB or AP-1 were constructed. Luciferase reporter assays demonstrate iE<jats:sub>\u03ba<\/jats:sub> is active in Ig\u03ba-expressing NPC cells and LMP1 expression can upregulate the activity of iE<jats:sub>\u03ba<\/jats:sub> in NPC cells. Mutation of the NF-\u03baB or AP-1 site within and downstream the iE<jats:sub>\u03ba<\/jats:sub>, inhibition of the NF-\u03baB and AP-1 pathways by their respective chemical inhibitor Bay11-7082 and SP600125 as well as stable or transient expression of dominant-negative mutant of I\u03baB\u03b1 (DNMI\u03baB\u03b1) or of c-Jun (TAM67) indicate that both sites are functional and LMP1-enhanced iE<jats:sub>\u03ba<\/jats:sub> activity is partly regulated by these two sites. Gel shift assays show that LMP1 promotes NF-\u03baB subunits p52 and p65 as well as AP-1 family members c-Jun and c-Fos binding to the \u03baNF-\u03baB and the \u03baAP-1 motifs <jats:italic>in vitro<\/jats:italic>, respectively. Both chemical inhibitors and dominant negative mutants targeting for NF-\u03baB and AP-1 pathways can attenuate the LMP1-enhanced bindings. Co-IP assays using nuclear extracts from HNE2-LMP1 cells reveal that p52 and p65, c-Jun and c-Fos proteins interact with each other at endogenous levels. ChIP assays further demonstrate p52 and p65 binding to the \u03baB motif as well as c-Jun and c-Fos binding to the AP-1 motif of Ig kappa gene <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These results suggest that human iE<jats:sub>\u03ba<\/jats:sub> is active in Ig\u03ba-expressing NPC cells and LMP1-stimulated NF-\u03baB and AP-1 activation results in an augmenting activation of the iE<jats:sub>\u03ba<\/jats:sub>. LMP1 promotes the interactions of heterodimeric NF-\u03baB (p52\/p65) and heterodimeric AP-1 (c-Jun\/c-Fos) transcription factors with the human iE<jats:sub>\u03ba<\/jats:sub> enhancer region are important for the upregulation of kappa light chain in LMP1-positive nasopharyngeal carcinoma cells.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1476-4598-8-92","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T19:14:15Z","timestamp":1256670855000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells"],"prefix":"10.1186","volume":"8","author":[{"given":"HaiDan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DuoSha","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SuFang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZiJian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiYun","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhenLian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,10,27]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.cellsig.2006.07.012","volume":"19","author":"HD Liu","year":"2007","unstructured":"Liu HD, Zheng H, Li M, Hu DS, Tang M, Cao Y: Upregulated expression of kappa light chain by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cells via NF-kappaB and AP-1 pathways. 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