FBP1 Is an Interacting Partner of Menin.

FBP1 Is an Interacting Partner of Menin.
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DOI:
10.1155/2014/535401
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发表时间:
2014
影响因子:
2.8
通讯作者:
Marx SJ
Marx SJ
中科院分区:
医学4区
文献类型:
--
作者:
Zaman S;Sukhodolets K;Wang P;Qin J;Levens D;Agarwal SK;Marx SJ

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多发性内分泌肿瘤1型(MEN1)是一种以甲状旁腺、垂体、肠胰神经内分泌组织等多个内分泌组织发生肿瘤为特征的综合征。 MEN1 通常是由编码 menin 蛋白的 MEN1 基因突变引起的。 Menin 与调节转录、DNA 修复和加工以及细胞骨架结构维护的蛋白质相互作用。我们描述了在大规模下拉测定中将 FBP1 鉴定为 menin 的相互作用伙伴,该测定还免疫沉淀 RBBP5、ASH2 和 LEDGF,这些都是与 SET1 (COMPASS) 相关的复杂蛋白的成员,SET1 是一种甲基化组蛋白 H3 的蛋白复合物。这种相互作用通过免疫共沉淀和 Flag-pull-down 测定得到证实。此外,menin 定位于 MYC 启动子上的 FUSE 位点,该位点由 FBP1 反式激活。因此,这项研究将 menin 置于调节 MYC 基因表达的途径中,并对 menin 的生物学功能具有重要意义。
Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors in multiple endocrine tissues such as the parathyroid glands, the pituitary gland, and the enteropancreatic neuroendocrine tissues. MEN1 is usually caused by mutations in the MEN1 gene that codes for the protein menin. Menin interacts with proteins that regulate transcription, DNA repair and processing, and maintenance of cytoskeletal structure. We describe the identification of FBP1 as an interacting partner of menin in a large-scale pull-down assay that also immunoprecipitated RBBP5, ASH2, and LEDGF, which are members of complex proteins associated with SET1 (COMPASS), a protein complex that methylates histone H3. This interaction was confirmed by coimmunoprecipitation and Flag-pull-down assays. Furthermore, menin localized to the FUSE site on the MYC promoter, a site that is transactivated by FBP1. This investigation therefore places menin in a pathway that regulates MYC gene expression and has important implications for the biological function of menin.
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