Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis
Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis
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DOI：
10.1038/ncb1415
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发表时间：
2006-06-01
影响因子：
21.3
通讯作者：
Baek, Sung Hee
中科院分区：
文献类型：
--
作者：
Kim, Jung Hwa;Choi, Hee June;Baek, Sung Hee
定义转录调控因子内的功能模块，控制阻遏和激活事件之间的转换是生物学的一个中心问题。最近，我们报道了β-连环蛋白-reptin染色质重塑复合物在调节转移抑制基因KAI 1中的动态作用（参考文献1），该基因能够抑制肿瘤转移的进展2 -5。在这里，我们确定的信号传导因子，赋予阻遏功能的reptin，从而抑制KAI 1的表达。含有reptin的复合物的生化纯化揭示了特异性去小泛素化酶的存在，该酶逆转reptin的小泛素化，该小泛素化是其作为阻遏物的功能的基础。reptin的去小泛素化改变了reptin的抑制功能及其与HDAC 1的关联。此外，reptin的SUMO化状态调节具有转移潜能的癌细胞的侵袭活性。这些数据清楚地定义了一个功能模型，并为SUMO修饰在癌症转移中提供了一个新的联系。
Defining the functional modules within transcriptional regulatory factors that govern switching between repression and activation events is a central issue in biology. Recently, we have reported the dynamic role of a beta-catenin-reptin chromatin remodelling complex in regulating a metastasis suppressor gene KAI1 (ref.1), which is capable of inhibiting the progression of tumour metastasis2-5. Here, we identify signalling factors that confer repressive function on reptin and hence repress the expression of KAI1. Biochemical purification of a reptin-containing complex has revealed the presence of specific desumoylating enzymes that reverse the sumoylation of reptin that underlies its function as a repressor. Desumoylation of reptin alters the repressive function of reptin and its association with HDAC1. Furthermore, the sumoylation status of reptin modulates the invasive activity of cancer cells with metastatic potential. These data clearly define a functional model and provide a novel link for SUMO modification in cancer metastasis.