Increased phosphorylation of histone H3 at serine 10 is involved in Epstein-Barr virus latent membrane protein-1-induced carcinogenesis of nasopharyngeal carcinoma.
Increased phosphorylation of histone H3 at serine 10 is involved in Epstein-Barr virus latent membrane protein-1-induced carcinogenesis of nasopharyngeal carcinoma.
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组蛋白 H3 丝氨酸 10 磷酸化增加参与 Epstein-Barr 病毒潜伏膜蛋白 1 诱导的鼻咽癌癌变
DOI：
10.1186/1471-2407-13-124
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发表时间：
2013-03-18
期刊：
影响因子：
3.8
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Li B;Huang G;Zhang X;Li R;Wang J;Dong Z;He Z
背景组蛋白H3磷酸化水平升高是肿瘤细胞转化的重要调控机制。我们的目的是探索组蛋白H3磷酸化在丝氨酸10方法应用免疫组化方法检测p-H3 Ser 10在鼻咽癌、慢性鼻咽炎及正常鼻咽组织中的表达，并与正常鼻咽组织进行比较，分析p-H3 Ser 10在EB病毒潜伏膜蛋白1（LMP 1）诱导鼻咽癌发生中的作用。并在鼻咽癌组织和细胞系中分析其与LMP 1的相关性。分别采用CCK-8法、焦点形成法和报告基因法检测组蛋白H3 Ser 10基序对LMP 1诱导的CNE 1细胞增殖、转化和激活蛋白-1（AP-1）激活的影响。用体外激酶活性测定法和蛋白质印迹法检测细胞中丝裂原活化激酶1（Mitogen activated kinase 1，MSK 1）和应激活化激酶1（stress activated kinase 1，MSK 1）的活性和磷酸化水平。结果低分化鼻咽癌组织中p-H3 Ser 10的表达明显高于慢性鼻咽炎（p<0.05）和正常鼻咽组织（p<0.001）;鼻咽癌组织和细胞株中p-H3 Ser 10的高表达与LMP 1的表达呈正相关（χ2= 6.700，p =0.01; C=0.350）。组蛋白H3的敲低和突变体（S10 A）抑制LMP 1诱导的CNE 1细胞增殖、灶形成和AP-1激活。此外，LMP 1还可增加MSK 1激酶活性和磷酸化。MSK 1抑制剂H89或通过siRNA敲低MSK 1可阻断LMP 1诱导的组蛋白H3丝氨酸10位磷酸化和AP-1激活。组蛋白H3丝氨酸10位磷酸化水平升高可能是LMP 1诱导鼻咽癌发生的重要调控机制。
BackgroundIncreased histone H3 phosphorylation is an essential regulatory mechanism for neoplastic cell transformation. We aimed to explore the role of histone H3 phosphorylation at serine10 (p-H3Ser10) in Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1)-induced carcinogenesis of nasopharyngeal carcinoma (NPC).MethodsThe expression of p-H3Ser10 was detected by the immunohistochemical analysis in NPC, chronic nasopharyngitis and normal nasopharynx tissues, and its correlation with LMP1 was analyzed in NPC tissues and cell lines. Using the small interfering RNA (siRNA)-H3 and histone H3 mutant (S10A), the effect of histone H3 Ser10 motif on LMP1-induced CNE1 cell proliferation, transformation and activator protein-1 (AP-1) activation were evaluated by CCK-8, focus-forming and reporter gene assay respectively. Mitogen- and stress-activated kinase 1 (MSK1) kinase activity and phosphorylation were detected byin vitrokinase assay and western blot. Using MSK1 inhibitor H89 or siRNA-MSK1, the regulatory role of MSK1 on histone H3 phosphorylation and AP-1 activation were analyzed.ResultsImmunohistochemical analysis revealed that the expression of p-H3Ser10 was significantly higher in the poorly differentiated NPC tissues than that in chronic nasopharyngitis (p<0.05) and normal nasopharynx tissues (p<0.001). Moreover, high level of p-H3Ser10 was positively correlated with the expression of LMP1 in NPC tissues (χ2=6.700,p=0.01; C=0.350) and cell lines. The knockdown and mutant (S10A) of histone H3 suppressed LMP1-induced CNE1 cell proliferation, foci formation and AP-1 activation. In addition, LMP1 could increase MSK1 kinase activity and phosphorylation. MSK1 inhibitor H89 or knockdown of MSK1 by siRNA blocked LMP1-induced phosphorylation of histone H3 at Ser10 and AP-1 activation.ConclusionEBV-LMP1 can induce phosphorylation of histone H3 at Ser10 via MSK1. Increased phosphorylation of histone H3 at Ser10 is likely a crucial regulatory mechanism involved in LMP1-induced carcinogenesis of NPC.
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影响因子：
5.4
作者：
MOORTHY, RK;THORLEYLAWSON, DA
通讯作者：
THORLEYLAWSON, DA
影响因子：
3.7
作者：
Lee, Soyoung;Horn, Virginie;Julien, Eric;Liu, Yi;Wysocka, Joanna;Bowerman, Bruce;Hengartner, Michael O.;Herr, Winship
通讯作者：
Herr, Winship
影响因子：
11.2
作者：
Drobic, B;Espino, PS;Davie, JR
通讯作者：
Davie, JR
DOI：
10.1083/jcb.60.2.356
发表时间：
1974-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gurley LR;Walters RA;Tobey RA
通讯作者：
Tobey RA
影响因子：
6
作者：
Horikawa, T;Sheen, TS;Yoshizaki, T
通讯作者：
Yoshizaki, T