TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization.
TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization.
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DOI：
10.4161/cc.23825
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发表时间：
2013-03-15
期刊：
影响因子：
--
通讯作者：
Cheung BB
中科院分区：
文献类型：
--
作者：
Bell JL;Malyukova A;Kavallaris M;Marshall GM;Cheung BB
神经母细胞瘤是儿童最常见的实体瘤，占所有儿童癌症死亡的15%。我们先前已经证明，三方基序16(TRIM16)是环B盒卷曲线圈(RBCC)/三方共轭(TRIM)蛋白家族的成员，在体外对神经母细胞瘤的增殖、迁移和体内致瘤性具有重要作用。然而，这种假定的肿瘤抑制因子影响细胞增殖和致瘤性的机制尚不确定。在这里，我们首次展示了TRIM16‘S在细胞周期进展和神经母细胞瘤发生发展过程中的显著表达模式和动态定位。在酪氨酸羟基酶MYCN(TH-MYCN)神经母细胞瘤小鼠模型中，免疫组织化学染色显示TRIM16在分化的神经节细胞中有强的核表达，而在肿瘤起始细胞中没有表达。此外，体外研究清楚地表明，在G1期，TRIM16蛋白的表达上调并向细胞核迁移。TRIM16还通过改变Cyclin D1和p27的表达在细胞周期进程中发挥作用。重要的是，利用TRIM16缺失突变体，发现TRIM16的一个未知蛋白结构域对TRIM16的S生长抑制作用及其核定位都是必需的。综上所述，我们的数据表明，TRIM16是神经母细胞瘤G1/S进展和细胞分化的新的调节因子。
Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children’s cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblastoma proliferation and migration in vitro and tumorigenicity in vivo. However, the mechanism by which this putative tumor suppressor influences cell proliferation and tumorigenicity was undetermined. Here we show, for the first time, TRIM16’s striking pattern of expression and dynamic localization during cell cycle progression and neuroblastoma tumor development. In a tyrosine hydroxylase MYCN (TH-MYCN) neuroblastoma mouse model, immunohistochemical staining revealed strong nuclear TRIM16 expression in differentiating ganglia cells but not in the tumor-initiating cells. Furthermore in vitro studies clearly demonstrated that during G1 cell cycle phase, TRIM16 protein expression is upregulated and shifts to the nucleus of cells. TRIM16 also plays a role in cell cycle progression through changes in Cyclin D1 and p27 expression. Importantly, using TRIM16 deletion mutants, an uncharacterized protein domain of TRIM16 was found to be required for both TRIM16’s growth inhibitory effects and its nuclear localization. Taken together, our data suggest that TRIM16 acts as a novel regulator of both neuroblastoma G1/S progression and cell differentiation.
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影响因子：
8
作者：
Marshall, G. M.;Bell, J. L.;Koach, J.;Tan, O.;Kim, P.;Malyukova, A.;Thomas, W.;Sekyere, E. O.;Liu, T.;Cunningham, A. M.;Tobias, V.;Norris, M. D.;Haber, M.;Kavallaris, M.;Cheung, B. B.
通讯作者：
Cheung, B. B.
影响因子：
8
作者：
Borriello, A;Della Pietra, V;Della Ragione, F
通讯作者：
Della Ragione, F
影响因子：
4.8
作者：
Beer, HD;Munding, C;Werner, S
通讯作者：
Werner, S
影响因子：
3.7
作者：
Bell JL;Malyukova A;Holien JK;Koach J;Parker MW;Kavallaris M;Marshall GM;Cheung BB
通讯作者：
Cheung BB
影响因子：
4
作者：
Kurki, S;Latonen, L;Laiho, M
通讯作者：
Laiho, M