DeSUMOylation of Gli1 by SENP1 Attenuates Sonic Hedgehog Signaling
DeSUMOylation of Gli1 by SENP1 Attenuates Sonic Hedgehog Signaling
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SENP1 对 Gli1 的去SUMO化会减弱 Sonic Hedgehog 信号传导
DOI：
10.1128/mcb.00579-16
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发表时间：
2017-09-01
影响因子：
5.3
通讯作者：
Cheng, Steven Y.
中科院分区：
文献类型：
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作者：
Liu, Huaize;Yan, Sen;Cheng, Steven Y.
Sonic Hedgehog形态发生途径的转录输出由三个Kruppel家族转录因子Gli1至-3调控，这些转录因子经历广泛的翻译后修饰，包括泛素化和sumo化。在这里，我们报道了SENP1特异性肽酶是Gli1特异性的去umoylation酶。我们发现SUMOylation通过与保守赖氨酸残基的泛素化竞争来稳定Gli1，并且SUMOylation的Gli1在细胞核中富集，这表明SUMOylation是Gli1的核定位信号。最后，我们发现小干扰RNA （siRNA）介导的SENP1的敲低增强了Shh维持小脑颗粒细胞前体增殖的能力，证明了SENP1负调控Shh信号的生理意义。
The transcriptional output of the Sonic Hedgehog morphogenic pathway is orchestrated by three Kruppel family transcription factors, Gli1 to -3, which undergo extensive posttranslational modifications, including ubiquitination and SUMOylation. Here, we report that the sentrin-specific peptidase SENP1 is the specific deSUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues and that SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1. Finally, we show that small interfering RNA (siRNA)-mediated knockdown of SENP1 augments the ability of Shh to sustain the proliferation of cerebellar granule cell precursors, demonstrating the physiological significance of the negative regulation of Shh signaling by SENP1.