Ladomery Michael R, Harper Steven J, Bates David O
Centre for Research in Biomedicine, Bristol Genomics Research Institute, Faculty of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK.
Cancer Lett. 2007 May 8;249(2):133-42. doi: 10.1016/j.canlet.2006.08.015. Epub 2006 Oct 5.
Alternative splicing, first discovered in the 1970s, has emerged as one of the key generators of proteomic diversity. Not surprisingly, alternative splicing is increasingly linked to the etiology of cancer. This is illustrated by vascular endothelial growth factor (VEGF), the dominant angiogenic factor. Recently, an antiangiogenic family of VEGF isoforms was discovered, and termed VEGF(xxx)b. VEGF(xxx)b isoforms arise from an alternative 3' splice site in exon 8, and differ by a mere six amino acids at the C-terminus. These alternative six amino acids radically change the functional properties of VEGF. VEGF(xxx)b isoform expression is regulated in human tissues and development, and disregulated in many pathological states including cancer. Understanding what regulates VEGF(xxx)b alternative splicing, and therefore the balance of pro- and antiangiogenic isoforms is of great importance and will be explored in detail over the next few years.
可变剪接最早于20世纪70年代被发现，现已成为蛋白质组多样性的关键产生机制之一。毫不奇怪，可变剪接与癌症病因的联系日益紧密。血管内皮生长因子（VEGF），即主要的血管生成因子，就说明了这一点。最近，发现了一个VEGF异构体的抗血管生成家族，称为VEGF(xxx)b。VEGF(xxx)b异构体源自外显子8中一个可变的3'剪接位点，仅在C端相差六个氨基酸。这六个可变氨基酸从根本上改变了VEGF的功能特性。VEGF(xxx)b异构体的表达在人体组织和发育过程中受到调控，而在包括癌症在内的许多病理状态下则失调。了解是什么调控了VEGF(xxx)b的可变剪接，进而了解促血管生成和抗血管生成异构体的平衡，具有重要意义，并将在未来几年进行详细探讨。
