Human cystathionine β-synthase is a target for sumoylation
Human cystathionine β-synthase is a target for sumoylation
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DOI：
10.1021/bi0615644
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发表时间：
2006-11-14
期刊：
影响因子：
2.9
通讯作者：
Banerjee, Ruma
中科院分区：
文献类型：
--
作者：
Kabil, Omer;Zhou, You;Banerjee, Ruma
胱硫醚β-合酶（CBS）催化转硫途径中的第一个不可逆步骤，并将毒性代谢产物同型半胱氨酸转化为半胱氨酸。CBS突变是严重遗传性高同型半胱氨酸血症的最常见原因。与CBS缺乏相关的器官特异性病理学的分子基础是未知的，CBS和亨廷顿蛋白之间的相互作用的重要性也是未知的。在这项研究中，我们使用酵母双杂交方法来筛选与CBS相互作用的蛋白质，并确定了sumoylation途径的几个组成部分，包括Ubc 9，PIAS 1，PIAS 3，Pc 2和RanBPM。我们证明，CBS是由小泛素样修饰剂-1蛋白（SUMO-I）在体外和体内条件下修改。CBS的缺失分析表明，C-末端调节结构域是与SUMO化机制中的蛋白质相互作用所必需的。SUMO化的CBS存在于细胞核中，在那里它与细胞核支架结合。CBS是类小泛素化的靶点的发现为这种酶的复杂调控增加了另一层，并揭示了这种蛋白质以前未知的住所，即，在细胞核中。
Cystathionine beta-synthase (CBS) catalyzes the first irreversible step in the transsulfuration pathway and commits the toxic metabolite, homocysteine, to the synthesis of cysteine. Mutations in CBS are the most common cause of severe hereditary hyperhomocysteinemia. The molecular basis of the organ-specific pathologies associated with CBS deficiency is unknown as is the significance of the reported interaction between CBS and Huntingtin protein. In this study, we have used the yeast two-hybrid approach to screen for proteins that interact with CBS and have identified several components of the sumoylation pathway including Ubc9, PIAS1, PIAS3, Pc2, and RanBPM. We demonstrate that CBS is modified by the small ubiquitin-like modifier-1 protein (SUMO-I) under both in vitro and in vivo conditions. Deletion analysis of CBS indicates that the C-terminal regulatory domain is required for interaction with proteins in the sumoylation machinery. Sumoylated CBS is present in the nucleus where it is associated with the nuclear scaffold. The discovery that CBS is a target of sumoylation adds another layer to the complex regulation of this enzyme and reveals a previously unknown residence for this protein, i.e., in the nucleus.