SPOP and CUL3 Modulate the Sonic Hedgehog Signal Response Through Controlled Degradation of GLI Family Transcription Factors.
SPOP and CUL3 Modulate the Sonic Hedgehog Signal Response Through Controlled Degradation of GLI Family Transcription Factors.
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SPOP和CUL3通过控制GLI家族转录因子的降解来调节Sonic Hedgehog信号响应。
DOI：
10.3389/fcell.2021.710295
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ogden SK
中科院分区：
文献类型：
--
作者：
Umberger PA;Ogden SK
斑点型POZ蛋白（SPOP）作为基因组完整性的守护者，并通过作为CUL3/ ring型E3泛素连接酶复合物的底物适配器来控制转录调控。含有spop的CUL3复合物靶向参与DNA修复和基因表达的无数DNA结合蛋白，因此是细胞稳态的重要调节剂。GLI转录因子是Hedgehog （HH）通路的效应因子，是组织形态发生和发育后稳态的关键驱动因子，在癌症中通常被破坏。CUL3-SPOP活性通过控制GLI家族成员的稳定性来调节HH转录反应的幅度和持续时间。SPOP和GLI在相分离的核液滴中共同富集，被认为是cul3介导的GLI泛素化和降解的热点。在果蝇中也存在类似的框架，其中刺猬诱导的MATH （meprin和traf同源）和BTB （bric bric brbrac, tramtrack, broad complex）结构域蛋白（HIB）靶向GLI同源Cubitus interruptus （Ci）进行cul3导向的蛋白水解。尽管具有这种功能上的保守性，HIB和SPOP参与果蝇和脊椎动物HH信号传导的分子机制是不同的。在这篇小型综述中，我们强调了两个系统之间的相似性，并讨论了GLI/Ci靶向的进化分歧，这有助于我们理解GLI转录码在健康和疾病中是如何由SPOP和CUL3控制的。
The speckle-type POZ protein (SPOP) functions as a guardian of genome integrity and controls transcriptional regulation by functioning as a substrate adaptor for CUL3/RING-type E3 ubiquitin ligase complexes. SPOP-containing CUL3 complexes target a myriad of DNA-binding proteins involved in DNA repair and gene expression, and as such, are essential modulators of cellular homeostasis. GLI transcription factors are effectors of the Hedgehog (HH) pathway, a key driver of tissue morphogenesis and post-developmental homeostasis that is commonly corrupted in cancer. CUL3-SPOP activity regulates amplitude and duration of HH transcriptional responses by controlling stability of GLI family members. SPOP and GLI co-enrich in phase separated nuclear droplets that are thought to serve as hot spots for CUL3-mediated GLI ubiquitination and degradation. A similar framework exists in Drosophila, in which the Hedgehog-induced MATH (meprin and traf homology) and BTB (bric à brac, tramtrack, broad complex) domain containing protein (HIB) targets the GLI ortholog Cubitus interruptus (Ci) for Cul3-directed proteolysis. Despite this functional conservation, the molecular mechanisms by which HIB and SPOP contribute to Drosophila and vertebrate HH signaling differ. In this mini-review we highlight similarities between the two systems and discuss evolutionary divergence in GLI/Ci targeting that informs our understanding of how the GLI transcriptional code is controlled by SPOP and CUL3 in health and disease.
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影响因子：
13.8
作者：
Arensdorf AM;Marada S;Ogden SK
通讯作者：
Ogden SK
影响因子：
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作者：
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