The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E.
The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E.
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DOI：
10.1083/jcb.200301106
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发表时间：
2004-03-29
期刊：
影响因子：
--
通讯作者：
Sendtner M
中科院分区：
文献类型：
--
作者：
Chittka A;Arevalo JC;Rodriguez-Guzman M;Pérez P;Chao MV;Sendtner M
雪旺细胞因子1（Schwann cell factor 1，SC 1）是一种p75神经营养因子受体相互作用蛋白，属于含有PR/SET结构域的锌指蛋白家族，受血清和神经营养因子的调节。SC 1显示出不同的细胞质和细胞核分布，其在细胞核中的存在与这些细胞核中缺乏溴脱氧尿苷（BrdU）密切相关。在这里，我们调查了潜在的转录活性的SC 1和分析其各个结构域的功能。我们表明，SC 1作为一个转录抑制剂时，它是拴在Gal 4 DNA结合域。抑制活性需要一种对抑制素A敏感的组蛋白去乙酰化酶（HDAC）活性，SC 1与HDAC 1、2和3形成复合物。SC 1的转录抑制需要其锌指结构域和PR结构域的存在。此外，这两个结构域参与了SC 1对BrdU掺入的有效阻断。锌指结构域也是指导SC 1的核定位所必需的。最后，SC 1抑制一个促有丝分裂基因，细胞周期蛋白E的启动子，这表明生长停滞是如何由SC 1调节的机制。
Schwann cell factor 1 (SC1), a p75 neurotrophin receptor–interacting protein, is a member of the positive regulatory/suppressor of variegation, enhancer of zeste, trithorax (PR/SET) domain-containing zinc finger protein family, and it has been shown to be regulated by serum and neurotrophins. SC1 shows a differential cytoplasmic and nuclear distribution, and its presence in the nucleus correlates strongly with the absence of bromodeoxyuridine (BrdU) in these nuclei. Here, we investigated potential transcriptional activities of SC1 and analyzed the function of its various domains. We show that SC1 acts as a transcriptional repressor when it is tethered to Gal4 DNA-binding domain. The repressive activity requires a trichostatin A–sensitive histone deacetylase (HDAC) activity, and SC1 is found in a complex with HDACs 1, 2, and 3. Transcriptional repression exerted by SC1 requires the presence of its zinc finger domains and the PR domain. Additionally, these two domains are involved in the efficient block of BrdU incorporation by SC1. The zinc finger domains are also necessary to direct SC1's nuclear localization. Lastly, SC1 represses the promoter of a promitotic gene, cyclin E, suggesting a mechanism for how growth arrest is regulated by SC1.
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