Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family.
Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family.
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DOI：
10.1186/2045-3701-2-13
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发表时间：
2012-04-20
影响因子：
7.5
通讯作者：
Hung MC
中科院分区：
文献类型：
--
作者：
Wang YN;Hung MC
越来越多的证据表明，包括许多类型的癌症在内的各种疾病都是由亚细胞蛋白定位和区室化的改变引起的。因此，这是值得扩大我们的知识，在亚细胞运输的蛋白质，如表皮生长因子受体（EGFR）和受体酪氨酸激酶的ErbB-2，这是高度表达和激活的人类恶性肿瘤，往往与预后不良。细胞表面EGFR的充分表征的运输通过内吞作用和内体分选被路由到溶酶体以进行降解或回到质膜以进行再循环。EGFR信号通路的一种新的核模式已被逐渐破译，其中EGFR在胞吞后从细胞表面穿梭到细胞核，并且在那里充当转录调节剂，传递信号，并且参与多种生物学功能，包括细胞增殖、肿瘤进展、DNA修复和复制以及化疗和放射抗性。内化的EGFR也可以从细胞表面转运到几个细胞内区室，如高尔基体、内质网和线粒体，以及细胞核。本文就EGFR核家族的功能及EGFR从细胞表面转运至细胞器的可能途径进行综述。更好地理解EGFR转运的分子机制将有助于阐明受体生物学和抗EGFR治疗的潜在治疗靶点，以供临床应用。
Accumulating evidence suggests that various diseases, including many types of cancer, result from alteration of subcellular protein localization and compartmentalization. Therefore, it is worthwhile to expand our knowledge in subcellular trafficking of proteins, such as epidermal growth factor receptor (EGFR) and ErbB-2 of the receptor tyrosine kinases, which are highly expressed and activated in human malignancies and frequently correlated with poor prognosis. The well-characterized trafficking of cell surface EGFR is routed, via endocytosis and endosomal sorting, to either the lysosomes for degradation or back to the plasma membrane for recycling. A novel nuclear mode of EGFR signaling pathway has been gradually deciphered in which EGFR is shuttled from the cell surface to the nucleus after endocytosis, and there, it acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and chemo- and radio-resistance. Internalized EGFR can also be transported from the cell surface to several intracellular compartments, such as the Golgi apparatus, the endoplasmic reticulum, and the mitochondria, in addition to the nucleus. In this review, we will summarize the functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles. A better understanding of the molecular mechanism of EGFR trafficking will shed light on both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application.
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影响因子：
7.8
作者：
Bao, JX;Wolpowitz, D;Role, LW;Talmage, DA
通讯作者：
Talmage, DA
影响因子：
3.3
作者：
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作者：
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DOI：
10.1016/j.ijrobp.2007.08.065
发表时间：
2008-01-01
影响因子：
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作者：
Dittmann, Klaus H.;Mayer, Claus;Rodemann, H. Peter
通讯作者：
Rodemann, H. Peter
影响因子：
4.8
作者：
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通讯作者：
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