Inhibition of DNA binding of Sox2 by the SUMO conjugation

Inhibition of DNA binding of Sox2 by the SUMO conjugation
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DOI:
10.1016/j.bbrc.2006.10.130
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发表时间:
2006-12-29
影响因子:
3.1
通讯作者:
Nakao, Mitsuyoshi
Nakao, Mitsuyoshi
中科院分区:
生物学4区
文献类型:
--
作者:
Tsuruzoe, Shu;Ishihara, Ko;Nakao, Mitsuyoshi

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Sox 2是高迁移率族(HMG)结构域DNA结合蛋白的成员,用于转录控制和染色质结构。Sox 2的HMG结构域结合DNA以促进协同转录因子如Oct 3/4的反式激活。我们报告,小鼠Sox 2的修饰SUMO在赖氨酸247。精氨酸取代的目标赖氨酸失去了sumoylation,但影响不大的转录潜力或核定位的Sox 2。与未修饰的形式相比,Sox 2融合SUMO-1没有增加转录通过Fgf 4增强子在Oct 3/4的存在下。此外,在赖氨酸247或羧基末端的SUMO-1缀合的Sox 2减少了与Fgf 4增强子的结合。这表明Sox 2类小泛素化通过削弱DNA结合来负调控其转录作用。(c)2006年爱思唯尔公司All rights reserved.
Sox2 is a member of the high mobility group (HMG) domain DNA-binding proteins for transcriptional control and chromatin architecture. The HMG domain of Sox2 binds the DNA to facilitate transactivation by the cooperative transcription factors such as Oct3/4. We report that mouse Sox2 is modified by SUMO at lysine 247. Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2. By contrast with the unmodified form, Sox2 fused to SUMO-1 did not augment transcription via the Fgf4 enhancer in the presence of Oct3/4. Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer. These indicate that Sox2 sumoylation negatively regulates its transcriptional role through impairing the DNA binding. (c) 2006 Elsevier Inc. All rights reserved.