Kim Jung Hwa, Choi Hee June, Kim Bogyou, Kim Mi Hyang, Lee Ji Min, Kim Ik Soo, Lee Moon Hee, Choi Soo Joon, Kim Keun Il, Kim Su-Il, Chung Chin Ha, Baek Sung Hee
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, South Korea.
Nat Cell Biol. 2006 Jun;8(6):631-9. doi: 10.1038/ncb1415. Epub 2006 May 14.
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 metastasis. 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.
确定在转录调节因子中控制抑制和激活事件之间转换的功能模块是生物学中的一个核心问题。最近，我们报道了β-连环蛋白-瑞ptin染色质重塑复合物在调节转移抑制基因KAI1（参考文献1）中的动态作用，该基因能够抑制肿瘤转移的进展。在这里，我们鉴定了赋予瑞ptin抑制功能从而抑制KAI1表达的信号因子。对含瑞ptin复合物的生化纯化揭示了特定去SUMO化酶的存在，这些酶可逆转瑞ptin的SUMO化，而SUMO化是其作为抑制因子功能的基础。瑞ptin的去SUMO化改变了瑞ptin的抑制功能及其与HDAC1的关联。此外，瑞ptin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，并为癌症转移中的SUMO修饰提供了新的联系。
