TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
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DOI：
10.1038/onc.2010.340
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发表时间：
2010-11-18
期刊：
影响因子：
8
通讯作者：
Cheung, B. B.
中科院分区：
文献类型：
--
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.
TRIM蛋白家族参与多种细胞过程，但通常以其功能所必需的关键蛋白质-蛋白质相互作用为特征。TRIM 16在不同的癌症类型中被诱导，当癌细胞被迫沿着分化途径进行时。我们已经确定TRIM 16是一种具有组蛋白乙酰化酶活性的DNA结合蛋白，它是类维生素A处理的癌细胞中维甲酸受体β2转录反应所必需的。在这项研究中，我们表明，过度表达TRIM 16减少神经母细胞瘤细胞的生长，增强维甲酸诱导的分化和体内致瘤性降低。TRIM 16仅在原发性人神经母细胞瘤肿瘤组织的分化的神经节细胞组分中表达。在神经母细胞瘤细胞中，TRIM 16直接与细胞质波形蛋白和细胞核E2 F1结合。TRIM 16降低细胞运动性，这需要波形蛋白的下调。维甲酸处理和强制过表达导致TRIM 16易位到细胞核，并结合和下调细胞复制所需的核E2 F1。这项研究首次证明了TRIM 16作为肿瘤抑制因子，通过与神经母细胞瘤细胞中的细胞质波形蛋白和细胞核E2 F1相互作用影响神经炎分化，细胞迁移和复制。
The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein–protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor β2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
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影响因子：
4.7
作者：
Mu, ZM;Le, XF;Chang, KS
通讯作者：
Chang, KS
DOI：
10.1016/j.bbrc.2007.06.036
发表时间：
2007-08-17
影响因子：
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作者：
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通讯作者：
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影响因子：
158.5
作者：
Matthay, KK;Villablanca, JG;Reynolds, CP
通讯作者：
Reynolds, CP