Interaction between the 2′-5′ oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1
Interaction between the 2′-5′ oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1
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2′-5′ 寡腺苷酸合成酶样蛋白 p59 OASL 与转录抑制因子甲基 CpG 结合蛋白 1 之间的相互作用
DOI：
10.1046/j.1432-1033.2003.03966.x
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发表时间：
2004-02-01
期刊：
影响因子：
--
通讯作者：
Justesen, J
中科院分区：
文献类型：
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作者：
Andersen, JB;Strandbygård, DJ;Justesen, J
人类 2'-5' 寡腺苷酸合成酶 (OAS) 形成干扰素诱导蛋白的保守家族，由四个基因组成：OAS1、OAS2、OAS3 和 2'-5' 寡腺苷酸合成酶样基因 (OASL)。当被双链 RNA 激活时，OAS1-3 将 ATP 聚合成 2'-5' 连接的寡腺苷酸； 2'-5'-连接的寡腺苷酸反过来又激活潜在的核糖核酸内切酶，降解病毒和细胞 RNA。相比之下，虽然 p59 OASL 蛋白与 OAS 家族高度同源（45% 同一性），但其 350 个氨基酸的 N 末端结构域缺乏 2'-5' 寡腺苷酸合成酶活性。 C 端 164 个氨基酸结构域与泛素串联重复序列 30% 同源，进一步区分了 p59 OASL 蛋白，并表明它具有与其他 OAS 家族成员不同的生物学作用。为了剖析 p59 OASL 的功能，我们利用酵母双杂交系统来鉴定相互作用的蛋白质。甲基 CpG 结合蛋白 1 (MBD1) 具有转录抑制蛋白的功能，被鉴定为强 p59 OASL 相互作用蛋白。有趣的是，与 p59 OASL 一样，MBD1 基因的转录也是由干扰素诱导的，表明这些基因受到协调调节。这种相互作用在体外和体内均得到证实，并被定位到 p59 OASL 的泛素样结构域。 p59 OASL-MBD1 相互作用是特异性的，因为 p59 OASL 不与任何其他 MBD 家族成员相互作用，并且 MBD1 不与 OAS1 相互作用。这些发现在干扰素刺激的细胞中将 p59 OASL 与 MBD1 转录控制联系起来，并为未来研究这种相互作用的功能作用提供了基础。
The human 2'-5' oligoadenylate synthetases (OAS) form a conserved family of interferon-induced proteins consisting of four genes: OAS1, OAS2, OAS3 and the 2'-5' oligoadenylate synthetase-like gene (OASL). When activated by double-stranded RNA, OAS1-3 polymerize ATP into 2'-5'-linked oligoadenylates; 2'-5'-linked oligoadenylates, in turn, activate a latent endoribonuclease that degrades viral and cellular RNAs. In contrast, while the p59 OASL protein is highly homologous to the OAS family (45% identity), its 350 amino acid N-terminal domain lacks 2'-5' oligoadenylate synthetase activity. A C-terminal 164 amino acid domain, which is 30% homologous to a tandem repeat of ubiquitin, further distinguishes the p59 OASL protein and suggests that it serves a biological role which is distinct from other OAS family members. To dissect the function of p59 OASL, we utilized the yeast two-hybrid system to identify interacting proteins. Methyl CpG-binding protein 1 (MBD1), which functions as a transcriptional repressor, was identified as a strong p59 OASL interactor. Interestingly, like p59 OASL, transcription of the MBD1 gene was induced by interferon, indicating that these genes are co-ordinately regulated. The interaction was confirmed in vitro and in vivo and was mapped to the ubiquitin-like domain of p59 OASL. The p59 OASL-MBD1 interaction was specific, because p59 OASL did not interact with any of the other MBD family members and MBD1 did not interact with OAS1. These findings link the p59 OASL with MBD1 transcriptional control in the context of an interferon-stimulated cell, and provide the basis for future studies to examine the functional role of this interaction.