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Epstein-Barr virus latent membrane protein 1 modulates epidermal growth factor receptor promoter activity in a nuclear factor kappa B-dependent manner.
Cell Signal. 2004 Jul; 16(7):781-90.CS

Abstract

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) oncoprotein may cause multiple cellular changes including the induction of epidermal growth factor receptor (EGFR) expression and activation of the NFkappaB transcription factor. LMP1 increases the levels of both EGFR protein and mRNA, but does not stabilize EGFR mRNA. Thus, the effects of LMP1 are likely to be mediated by the direct activation of the EGFR promoter. In this study, induction of LMP1 increased the EGFR in both protein and promoter levels in a dose-dependent manner using tetracycline-regulated LMP1 expression in nasopharyngeal carcinoma (NPC) cell line. Mutational analysis of the LMP1 protein indicated that the C-terminal activation region-1 (CTAR1) domain was mainly involved in the EGFR promoter induction, while CTAR2 was necessary but not sufficient to induce EGFR promoter. Inhibition of LMP1-mediated NFkappaB activation by constitutive repressive IkappaBalpha marginally decreased EGFR promoter activity using transiently transfected IkappaBalpha dominant negative mutant. Promoter mutagenesis analysis demonstrated that two putative NFkappaB binding sites of EGFR promoter were very necessary for the transcriptional activity of EGFR induced by LMP1, the proximal NFkappaB binding site was more important than the distal NFkappaB binding site, and both NFkappaB binding sites played a cooperative role. Taken together, Epstein-Barr virus latent membrane protein 1 modulated the EGFR promoter activity in a NFkappaB-dependent manner.

Authors+Show Affiliations

Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15115657

Citation

Tao, Yong-Guang, et al. "Epstein-Barr Virus Latent Membrane Protein 1 Modulates Epidermal Growth Factor Receptor Promoter Activity in a Nuclear Factor Kappa B-dependent Manner." Cellular Signalling, vol. 16, no. 7, 2004, pp. 781-90.
Tao YG, Tan YN, Liu YP, et al. Epstein-Barr virus latent membrane protein 1 modulates epidermal growth factor receptor promoter activity in a nuclear factor kappa B-dependent manner. Cell Signal. 2004;16(7):781-90.
Tao, Y. G., Tan, Y. N., Liu, Y. P., Song, X., Zeng, L., Gu, H. H., Tang, M., Li, W., Yi, W., & Cao, Y. (2004). Epstein-Barr virus latent membrane protein 1 modulates epidermal growth factor receptor promoter activity in a nuclear factor kappa B-dependent manner. Cellular Signalling, 16(7), 781-90.
Tao YG, et al. Epstein-Barr Virus Latent Membrane Protein 1 Modulates Epidermal Growth Factor Receptor Promoter Activity in a Nuclear Factor Kappa B-dependent Manner. Cell Signal. 2004;16(7):781-90. PubMed PMID: 15115657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epstein-Barr virus latent membrane protein 1 modulates epidermal growth factor receptor promoter activity in a nuclear factor kappa B-dependent manner. AU - Tao,Yong-Guang, AU - Tan,Yun-Nian, AU - Liu,Yi-Ping, AU - Song,Xin, AU - Zeng,Liang, AU - Gu,Huang-Hua, AU - Tang,Ming, AU - Li,Wei, AU - Yi,Wei, AU - Cao,Ya, PY - 2003/11/14/received PY - 2003/12/01/revised PY - 2003/12/02/accepted PY - 2004/4/30/pubmed PY - 2004/12/17/medline PY - 2004/4/30/entrez SP - 781 EP - 90 JF - Cellular signalling JO - Cell Signal VL - 16 IS - 7 N2 - The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) oncoprotein may cause multiple cellular changes including the induction of epidermal growth factor receptor (EGFR) expression and activation of the NFkappaB transcription factor. LMP1 increases the levels of both EGFR protein and mRNA, but does not stabilize EGFR mRNA. Thus, the effects of LMP1 are likely to be mediated by the direct activation of the EGFR promoter. In this study, induction of LMP1 increased the EGFR in both protein and promoter levels in a dose-dependent manner using tetracycline-regulated LMP1 expression in nasopharyngeal carcinoma (NPC) cell line. Mutational analysis of the LMP1 protein indicated that the C-terminal activation region-1 (CTAR1) domain was mainly involved in the EGFR promoter induction, while CTAR2 was necessary but not sufficient to induce EGFR promoter. Inhibition of LMP1-mediated NFkappaB activation by constitutive repressive IkappaBalpha marginally decreased EGFR promoter activity using transiently transfected IkappaBalpha dominant negative mutant. Promoter mutagenesis analysis demonstrated that two putative NFkappaB binding sites of EGFR promoter were very necessary for the transcriptional activity of EGFR induced by LMP1, the proximal NFkappaB binding site was more important than the distal NFkappaB binding site, and both NFkappaB binding sites played a cooperative role. Taken together, Epstein-Barr virus latent membrane protein 1 modulated the EGFR promoter activity in a NFkappaB-dependent manner. SN - 0898-6568 UR - https://www.unboundmedicine.com/medline/citation/15115657/Epstein_Barr_virus_latent_membrane_protein_1_modulates_epidermal_growth_factor_receptor_promoter_activity_in_a_nuclear_factor_kappa_B_dependent_manner_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898656803002420 DB - PRIME DP - Unbound Medicine ER -