Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription
Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription
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DOI：
10.1016/s0092-8674(00)80967-8
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发表时间：
1999-01-08
期刊：
影响因子：
64.5
通讯作者：
Burns, AL
中科院分区：
文献类型：
--
作者：
Agarwal, SK;Guru, SC;Burns, AL
MEN 1是一种肿瘤抑制基因，编码一种610个氨基酸的核蛋白（menin），其功能以前未知。使用酵母双杂交筛选与menin作为诱饵，我们已经确定了转录因子JunD作为一个直接的menin相互作用的合作伙伴。Menin没有直接与Jun和Fos的其他家庭成员互动。在体外和体内证实了menin-JunD相互作用。Menin抑制由JunD融合到Gal 4 DNA结合结构域介导的转录激活，或由JunD从AP 1响应报告。几个自然发生的和成簇的MEN 1错义突变破坏了menin与JunD的相互作用。这些观察结果表明，menin的肿瘤抑制功能涉及直接结合到JunD和抑制JunD激活的转录。
MEN1 is a tumor suppressor gene that encodes a 610 amino acid nuclear protein (menin) of previously unknown function. Using a yeast two-hybrid screen with menin as the bait, we have identified the transcription factor JunD as a direct menin-interacting partner. Menin did not interact directly with other Jun and Fos family members. The menin-JunD interaction was confirmed in vitro and in vive. Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. Several naturally occurring and clustered MEN1 missense mutations disrupted menin interaction with JunD. These observations suggest that menin's tumor suppressor function involves direct binding to JunD and inhibition of JunD activated transcription.