Putative Roles of SETBP1 Dosage on the SET Oncogene to Affect Brain Development.
Putative Roles of SETBP1 Dosage on the SET Oncogene to Affect Brain Development.
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DOI：
10.3389/fnins.2022.813430
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发表时间：
2022
影响因子：
4.3
通讯作者：
Ernst, Carl
中科院分区：
文献类型：
--
作者：
Antonyan, Lilit;Ernst, Carl
SET结合蛋白1（SETBP 1）的突变导致两种不同的临床上可区分的疾病，称为Schinzel-Giedion综合征（SGS）或SETBP 1缺乏综合征（SDD）。这两种疾病都是蛋白质剂量的疾病，其中SGS是由蛋白质分解速率降低引起的，蛋白质分解速率降低是由于蛋白质体靶向结构域中的突变引起的，SDD是由杂合功能丧失突变引起的，导致单倍不足。虽然受影响个体的表型支持SETBP 1在大脑发育中的作用，但对可能导致这种情况的机制知之甚少。给予SETBP 1其名称的结合配偶体是SET，并且有关于非神经组织中的这种重要癌基因的大量文献。在这里，我们描述了不同的分子复合物，其中SET参与以及这些复合物在大脑发育中的作用。基于这些信息，我们假设SETBP 1蛋白剂量如何影响这些包含SET的分子通路并影响大脑发育。我们研究了SET和SETBP 1在乙酰化抑制、磷酸酶活性、DNA修复和细胞周期控制中的作用。这项工作为改变SETBP 1蛋白剂量如何影响大脑发育提供了可验证的假设。
Mutations in SET BINDING PROTEIN 1 (SETBP1) cause two different clinically distinguishable diseases called Schinzel–Giedion syndrome (SGS) or SETBP1 deficiency syndrome (SDD). Both disorders are disorders of protein dosage, where SGS is caused by decreased rate of protein breakdown due to mutations in a proteosome targeting domain, and SDD is caused by heterozygous loss-of-function mutations leading to haploinsufficiency. While phenotypes of affected individuals support a role for SETBP1 in brain development, little is known about the mechanisms that might underlie this. The binding partner which gave SETBP1 its name is SET and there is extensive literature on this important oncogene in non-neural tissues. Here we describe different molecular complexes in which SET is involved as well as the role of these complexes in brain development. Based on this information, we postulate how SETBP1 protein dosage might influence these SET-containing molecular pathways and affect brain development. We examine the roles of SET and SETBP1 in acetylation inhibition, phosphatase activity, DNA repair, and cell cycle control. This work provides testable hypotheses for how altered SETBP1 protein dosage affects brain development.
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影响因子：
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作者：
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DOI：
10.1073/pnas.1809682115
发表时间：
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