Nuclear localization of EGF receptor and its potential new role as a transcription factor
Nuclear localization of EGF receptor and its potential new role as a transcription factor
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DOI：
10.1038/ncb0901-802
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发表时间：
2001-09-01
影响因子：
21.3
通讯作者：
Hung, MC
中科院分区：
文献类型：
--
作者：
Lin, SY;Makino, K;Hung, MC
表皮生长因子受体（EGFR）在许多组织和细胞系的细胞核中被检测到。然而，核EGFR的潜在功能在很大程度上被忽视了。在这里，我们证明，核EGFR与组织的高度增殖活动密切相关。当EGFR与GAL4 DNA结合域融合时，我们发现EGFR的羧基端含有一个强的反式激活结构域。此外，该受体复合物结合并激活AT丰富的共有序列依赖性转录，包括cyclin D1启动子中的共有位点。通过染色质免疫沉淀分析，我们进一步证明了细胞核EGFR与细胞周期蛋白D1的启动子区在体内相关。因此，EGFR可能作为转录因子激活高度增殖活动所需的基因。
Epidermal growth factor receptor (EGFR) has been detected in the nucleus in many tissues and cell lines. However, the potential functions of nuclear EGFR have largely been overlooked. Here we demonstrate that nuclear EGFR is strongly correlated with highly proliferating activities of tissues. When EGFR was fused to the GAL4 DNA-binding domain, we found that the carboxy terminus of EGFR contained a strong transactivation domain. Moreover, the receptor complex bound and activated AT rich consensus-sequence-dependent transcription, including the consensus site in cyclin Dl promoter. By using chromatin immunoprecipitation assays, we further demonstrated that nuclear EGFR associated with promoter region of cyclin D1 in vivo. EGFR might therefore function as a transcription factor to activate genes required for highly proliferating activities.