Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the ETS protein ER71
Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the ETS protein ER71
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DOI：
10.1002/jcb.20945
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发表时间：
2006-09-01
影响因子：
4
通讯作者：
Janknecht, Ralf
中科院分区：
文献类型：
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作者：
Knebel, Julia;De Haro, Luciano;Janknecht, Ralf
睾丸特异性基因A（Testis-specific gene A，TSGA）最初在大鼠中被鉴定，并显示在睾丸内表达。在这里，我们克隆了小鼠同源物[也称为jumonji结构域包含la（Jmjd 1a）]，并首次表征了TSGA蛋白及其功能。虽然小鼠TSGA在睾丸中表达，但其mRNA也存在于许多其他组织中，包括心脏、胸腺、肝脏和皮肤。免疫组化显示TSGA是一种核蛋白，其N端含有一个推测的核定位信号。TSGA显示出与疑似肿瘤抑制因子和辅激活因子（5 qNCA）、甲状腺激素受体相互作用蛋白（TRIP 8）和辅抑制因子Hairless的显著同源性，这表明TSGA在转录调节中的作用。事实上，TSGA含有几个功能性转录抑制结构域。此外，TSGA在体外和体内与ER 71（ETS相关71）相互作用，ER 71是一种在成年小鼠睾丸中和胚胎发生期间表达的转录因子。具体地，TSGA的N-末端和ER 71的C-末端主要参与它们的复合物形成。此外，TSGA损害ER 71激活基质金属蛋白酶-1启动子转录的能力。因此，TSGA可以调节ER 71的功能，从而影响精子发生以及胚胎发育。
Testis-specific gene A (TSGA) was originally identified in rat and shown to be expressed within the testes. Here, we have cloned the murine homolog [also known as jumonji domain-containing la (Jmjd1a)] and for the first time characterized the TSGA protein and its functions. Although murine TSGA is expressed in testes, its mRNA is also present in many other tissues, including heart, thymus, liver, and skin. Immunostaining revealed that TSGA is a nuclear protein, whose N-terminus contains a putative nuclear localization signal. TSGA displays significant homology to a suspected tumor suppressor and coactivator (5qNCA), to a thyroid hormone receptor interacting protein (TRIP8) and to the corepressor Hairless, pointing at a role of TSGA in transcription regulation. Indeed, TSGA contains several functional transcription repression domains. In addition, TSGA interacts both in vitro and in vivo with ER71 (ETS related 71), a transcription factor that is expressed in the testes of adult mice and during embryogenesis. Specifically, the N-terminus of TSGA and the C-terminus of ER71 are primarily engaged in their complex formation. Furthermore, TSGA impairs the ability of ER71 to activate transcription from the matrix metalloproteinase-1 promoter. Thus, TSGA may modulate the function of ER71 and thereby affect spermatogenesis as well as embryonic development.