Selenocysteine Machinery Primarily Supports TXNRD1 and GPX4 Functions and Together They Are Functionally Linked with SCD and PRDX6.
Selenocysteine Machinery Primarily Supports TXNRD1 and GPX4 Functions and Together They Are Functionally Linked with SCD and PRDX6.
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DOI：
10.3390/biom12081049
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发表时间：
2022-07-28
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
人类基因组有25个编码含硒半胱氨酸（Sec）蛋白的基因，其合成由专门的Sec机器蛋白支持。在这里，我们进行了分析的co-essentiality网络，以确定功能的合作伙伴的硒蛋白和Sec机械。一个突出的集群包括所有七个已知的Sec机器蛋白和两个关键的硒蛋白，GPX 4和TXNRD 1。此外，这9个基因进一步与PRDX 6正相关，与SCD负相关，将后两个基因与硒的重要作用联系起来。我们分析了一千个癌细胞系中基因敲除的必要性分数，发现Sec代谢基因对一部分原发组织具有强烈的选择性，这表明某些癌细胞系特别依赖于硒。一个单独的突出集群包括硒磷酸合成酶SEPHS 1，它与一组转录因子相关联，而其余的硒蛋白既不与这些集群相关联，也不相互关联。这些数据表明，SEC机制的关键组成部分已经被确定，它们的主要作用是支持GPX 4和TXNRD 1的功能，并与PRDX 6和SCD有进一步的功能联系。
The human genome has 25 genes coding for selenocysteine (Sec)-containing proteins, whose synthesis is supported by specialized Sec machinery proteins. Here, we carried out an analysis of the co-essentiality network to identify functional partners of selenoproteins and Sec machinery. One outstanding cluster included all seven known Sec machinery proteins and two critical selenoproteins, GPX4 and TXNRD1. Additionally, these nine genes were further positively associated with PRDX6 and negatively with SCD, linking the latter two genes to the essential role of selenium. We analyzed the essentiality scores of gene knockouts in this cluster across one thousand cancer cell lines and found that Sec metabolism genes are strongly selective for a subset of primary tissues, suggesting that certain cancer cell lineages are particularly dependent on selenium. A separate outstanding cluster included selenophosphate synthetase SEPHS1, which was linked to a group of transcription factors, whereas the remaining selenoproteins were linked neither to these clusters nor among themselves. The data suggest that key components of Sec machinery have already been identified and that their primary role is to support the functions of GPX4 and TXNRD1, with further functional links to PRDX6 and SCD.
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通讯作者：
Conrad M
DOI：
10.3390/antiox10060946
发表时间：
2021-06-11
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
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作者：
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通讯作者：
Lowther WT