Department of Medical Biochemistry and Genetics and MediCity Research Laboratory, University of Turku, Turku, Finland.
Cell Cycle. 2011 Aug 15;10(16):2647-57. doi: 10.4161/cc.10.16.17194.
Alternative splicing is a central tool of evolution that significantly increases the size of transcriptomes and generates functional specification. Within the human ERBB receptor gene family, only ERBB4 is known to produce functionally distinct isoforms as a result of alternative splicing. While ErbB4 signaling has been demonstrated to regulate cellular processes involved in embryogenesis, carcinogenesis and cardiovascular and psychiatric diseases, relatively little is known about the contribution of the individual isoforms in the different biological contexts. Here, we review recent findings as well as provide novel data about the distribution and functions of the ERBB4 splice variants. These observations represent an example of how minor alterations in the transcripts of a single gene can result in even antagonistic cellular responses. The observations also underline the significance of understanding the unique functions of isoforms of a potential drug target gene.
选择性剪接是进化的重要工具，可显著增加转录组的大小并产生功能特异性。在人类 ERBB 受体基因家族中，只有 ERBB4 已知由于选择性剪接而产生功能不同的异构体。虽然已经证明 ErbB4 信号传导可调节胚胎发生、致癌作用以及心血管和精神疾病中涉及的细胞过程，但对于不同生物学背景下各个异构体的贡献相对知之甚少。在这里，我们回顾了最近的发现，并提供了有关 ERBB4 剪接变体分布和功能的新数据。这些观察结果代表了单个基因的转录本中的微小变化如何导致甚至相反的细胞反应的一个例子。这些观察结果还强调了理解潜在药物靶标基因的异构体的独特功能的重要性。
