Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor
Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger protein and androgen receptor
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DOI：
10.1099/vir.0.014241-0
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发表时间：
2010-06-01
影响因子：
3.8
通讯作者：
Mueller-Lantzsch, Nikolaus
中科院分区：
文献类型：
--
作者：
Kaufmann, Sabine;Sauter, Manes;Mueller-Lantzsch, Nikolaus
人类基因组中存在超过2000种人类内源性逆转录病毒（HERV）序列，但只有少数是完整的并能够产生蛋白质。这些蛋白的正常功能（如果有的话）尚不清楚，但一些HERV蛋白与癌症，特别是生殖细胞癌症有关。例如，已经证明（i）生殖细胞肿瘤患者经常产生针对HERV蛋白的抗体，（ii）表达HERV-K（HML-2）rec的转基因小鼠易于发生原位睾丸癌，以及（iii）Rec可以结合并抑制生殖系干细胞多能性的监护人，早幼粒细胞白血病锌指蛋白（PLZF）本研究鉴定了PLZF相关的睾丸锌指蛋白（TZFP）作为HERV-K（HML-2）的结合伴侣Rec相互作用通过Rec的N-和C-末端结构域和TZFP的C-末端DNA结合锌指结构域（aa 375-450）发生。关于TZFP的功能知之甚少。该蛋白主要在睾丸中表达，在睾丸中作为转录抑制因子发挥作用，在精子发生的特定阶段活跃。TZFP的最深入研究的功能是活化的雄激素受体（AR）的共阻遏物。这里，显示Rec可以与TZFP和AR形成三聚体复合物，并且可以解除TZFP介导的对AR诱导的反式激活的阻遏。此外，Rec能够在报告基因测定中克服c-myc基因启动子的TZFP的直接转录阻遏。因此，HERV-K（HML-2）Rec可能通过去抑制致癌转录因子（如AR）发挥癌蛋白的作用。
More than 2000 human endogenous retrovirus (HERV) sequences are present in the human genome, yet only a few are intact and able to produce proteins. The normal functions of these, if any, are unknown, but some HERV proteins have been implicated in cancers, in particular germ-cell cancers. For instance, it has been documented that (i) patients with germ-cell tumours frequently produce antibodies against HERV proteins, (ii) transgenic mice expressing HERV-K (HML-2) rec are prone to testicular carcinoma in situ, and (iii) Rec can bind and suppress a guardian of germline stem-cell pluripotency, the promyelocytic leukaemia zinc-finger protein (PLZF) This study identified the PLZF-related testicular zinc-finger protein (TZFP) as a binding partner of HERV-K (HML-2) Rec Interactions occurred via the N- and C-terminal domains of Rec and the C-terminal DNA-binding zinc-finger domain of TZFP (aa 375-450). Not much is known about the function of TZFP The protein is expressed predominantly in the testis, where it functions as a transcriptional repressor that is active during specific stages of spermatogenesis. The most intensely studied function of TZFP is that of a co-repressor of the activated androgen receptor (AR) Here, it was shown that Rec can form a trimeric complex with TZFP and AR, and can relieve the TZFP-mediated repression of AR-induced transactivation In addition, Rec was able to overcome the direct transcriptional repression by TZFP of the c-myc gene promoter in reporter assays Thus, HERV-K (HML-2) Rec may function as an oncoprotein by de-repressing oncogenic transcription factors such as AR.