Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases

Li, Lili; Guo, Lili; Tao, Yongguang; Zhou, Shanghui; Wang, Zhenlian; Luo, Wei; Hu, Duosha; Li, Zijian; Xiao, Lanbo; Tang, Min; Yi, Wei; Tsao, Sai Wah; Cao, Yang

doi:10.1016/j.canlet.2007.04.014

Cited by 56 publications

(49 citation statements)

References 55 publications

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“…5B). High level of TP53 has been suggested to be related to EBV as previously discussed (9,40,45). In regard to the apoptosis pathway, although BCL2 acts as an antiapoptosis protein by inhibiting BAX, upregulation of BAX seems to lessen the effect of BCL2.…”

Section: Discussionmentioning

confidence: 89%

“…Although p53 levels are high in NPC, the mutation of TP53 gene is relatively rare. Accumulated p53 in NPC is believed to be mediated by EBV LMP1 (9,40,45). Two reasons have been proposed to explain why wild-type p53 fails to induce apoptosis in NPC: low ARF levels due to promoter hypermethylation and excess mutated p63.…”

Section: The Inferred Npc Network Consists Of Highly Interactive Cliqmentioning

confidence: 99%

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From NPC Therapeutic Target Identification to Potential Treatment Strategy

Lan

Chen

Lin

et al. 2010

Molecular Cancer Therapeutics

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Nasopharyngeal carcinoma (NPC) is relatively rare in Western countries but is a common cancer in southern Asia. Many differentially expressed genes have been linked to NPC; however, how to prioritize therapeutic targets and potential drugs from unsorted gene lists remains largely unknown. We first collected 558 upregulated and 993 downregulated NPC genes from published microarray data and the primary literatures. We then postulated that conversion of gene signatures into the protein-protein interaction network and analyzing the network topologically could provide insight into key regulators involved in tumorigenesis of NPC. Of particular interest was the presence of cliques, called fully connected subgraphs, in the inferred NPC networks. These clique-based hubs, connecting with more than three queries and ranked higher than other nodes in the NPC protein-protein interaction network, were further narrowed down by pathway analysis to retrieve 24 upregulated and 6 downregulated bottleneck genes for predicting NPC carcinogenesis. Moreover, additional oncogenes, tumor suppressor genes, genes involved in protein complexes, and genes obtained after functional profiling were merged with the

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Section: Discussionmentioning

confidence: 89%

Section: The Inferred Npc Network Consists Of Highly Interactive Cliqmentioning

confidence: 99%

From NPC Therapeutic Target Identification to Potential Treatment Strategy

Lan

Chen

Lin

et al. 2010

Molecular Cancer Therapeutics

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“…Modification of the p53 phosphorylation has been proposed to play a critical role in the stabilization and activation of p53. Li et al reported that p53 could be activated and phosphorylated clearly at Ser15, Ser20, Ser392, and Thr81 modulated by LMP1 (48). Further experiments are needed to elucidate the exact role of these proteins in possible p53 overexpression and stabilization.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpressed p53 protein is believed to have impaired tumor suppressor activity and to contribute to immortalization and cellular transformation (17,19,20). Until now, the activity of overexpressed p53 in the NPC remains unclear and the role of the p53 in NPC is INTERNATIONAL JOURNAL OF ONCOLOGY 34: 1017-1027, 2009 …”

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confidence: 99%

Functional characterization of p53 in nasopharyngeal carcinoma by stable shRNA expression

Sun

Yi²,

Yang³

et al. 2009

Int J Oncol

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Abstract. Nasopharyngeal carcinoma (NPC) is a highincidence malignancy in Southern China and Southeast Asia. Although mutation of p53 tumor-suppressor gene is a rare event in NPC, NPC has a high frequency of over-expressed/ accumulated p53 protein, which was reported to be dysfunction or inactivation in most of NPC. We report here a functional characterization of p53 in an undifferentiated NPC cell line CNE2. To elucidate the biological function of p53, we employed the RNA interference (RNAi) approach to knockdown the endogenously expressed p53 in CNE2 cells. Interestingly, suppression of p53 expression in CNE2 cells was associated with significant down-regulation of p21 WAF1/CIP1 expression and decreased HDM2 protein level in both steady state and genotoxic stress induced by ionizing radiation (IR). Consistent with these biochemical data were the accelerated cell cycle progression and the increased proliferation rate, suggesting that p53 retained growth inhibitory activity in CNE2 cells. Indeed, down-regulation of p53 in CNE2 enhanced the ability of CNE2 cells to grow anchorage-independently in vitro and to develop tumors in vivo. Together with the radioresistance acquired by CNE2sip53 cells, our data indicate that in contrast to a previous study, p53 in this NPC cell line remains functional, which may have an important therapeutical implication. IntroductionNasopharyngeal carcinoma (NPC) is featured by a remarkable racial and geographic distribution, and is a high-incidence malignancy in Southern China, Southeast Asia, Northern Africa, and Alaska, where the observed incidence rates range from 15 to 50 per 100,000 persons (1-3). NPC can occur in all age groups, but has a bimodal age distribution. The incidence peaks at 50 to 60 years of age; and a small peak is observed during late childhood (3). As an etiologically multi-factorial disease, carcinogenesis of the nasopharynx may result from combined effects of Epstein-Barr viral (EBV), genetic and environmental factors (4-7). Available information on the origin of NPC suggests that genetic alterations of tumor suppressor genes and proto-oncogenes in multiple cellular pathways may be important in multistage NPC carcinogenesis.p53 tumor-suppressor protein plays a pivotal role in regulating cell cycle, differentiation and apoptosis (8). As a transcription factor, p53 can induce the expression of p21 WAF1/CIP1 , which inhibits cyclin-dependent kinases, thereby preventing the phosphorylation of Rb and subsequent cell cycle arrest (9). Mutation of p53 tumor-suppressor gene has been found to be the most frequent genetic alteration in human malignancy. p53 mutations often result in accumulation of the mutant p53 protein, which either loses tumor suppressor function or gains oncogenic activity (10). p53 can also be functionally inactivated by mechanisms other than gene mutation (10). Screen for p53 mutations in the hot-spots for mutation revealed only a low frequency of p53 mutations ranging from 0 to 10%, which might explain the initial high sensitivity observed with ci...

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“…Another study has indicated that LMP1 can activate MAPK kinases to modulate p53 phosphorylation (167). The p53 gene mutation rate was significantly lower in NPC than in other cancers (192,238,282).…”

Section: The Molecular Mechanisms Of Ebv Infection and The Effects Onmentioning

confidence: 99%

Potential Therapeutic Molecular Targets for Nasopharyngeal Carcinoma

Chen¹

2012

Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

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Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases

Cited by 56 publications

References 55 publications

From NPC Therapeutic Target Identification to Potential Treatment Strategy

From NPC Therapeutic Target Identification to Potential Treatment Strategy

Functional characterization of p53 in nasopharyngeal carcinoma by stable shRNA expression

Potential Therapeutic Molecular Targets for Nasopharyngeal Carcinoma

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