SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells
SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells
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DOI：
10.1038/nsmb1185
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发表时间：
2007-01-01
影响因子：
16.8
通讯作者：
Wei, Li-Na
中科院分区：
文献类型：
--
作者：
Park, Sung Wook;Hu, Xinli;Wei, Li-Na
Tr2孤儿核受体可以被summoylated，导致其内源性靶基因Oct4调控区募集的共调节因子被替换。unsummoylated Tr2激活Oct4，促进胚胎癌细胞增殖，并定位于早幼粒细胞白血病（Pml）核体。当其丰度升高时，Tr2在Lys238处被SUMOylated，并似乎从核体中释放出来，起到抑制作用。Tr2的sumo化诱导其共调节因子的交换：共抑制因子Rip140取代共激活因子Pcaf，将Tr2从激活因子转换为抑制因子。这涉及到将Tr2动态分区为包含pml的池和不包含pml的池。这些结果支持了一个模型，其中sumoylation依赖性的分配和差异的共调节因子募集有助于维持激活Tr2的稳态供应，而不是抑制Tr2，从而微调Oct4表达并调节干细胞增殖。
The Tr2 orphan nuclear receptor can be SUMOylated, resulting in the replacement of coregulators recruited to the regulatory region of its endogenous target gene, Oct4. UnSUMOylated Tr2 activates Oct4, enhancing embryonal carcinoma-cell proliferation, and is localized to the promyelocytic leukemia ( Pml) nuclear bodies. When its abundance is elevated, Tr2 is SUMOylated at Lys238 and seems to be released from the nuclear bodies to act as a repressor. SUMOylation of Tr2 induces an exchange of its coregulators: corepressor Rip140 replaces coactivator Pcaf, which switches Tr2 from an activator to a repressor. This involves dynamic partitioning of Tr2 into Pml-containing and Pml-free pools. These results support a model where SUMOylation-dependent partitioning and differential coregulator recruitment contribute to the maintenance of a homeostatic supply of activating, as opposed to repressive, Tr2, thus fine-tuning Oct4 expression and regulating stem-cell proliferation.