CRUK Clinical Centre at Leeds, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
Adv Exp Med Biol. 2009;656:41-50. doi: 10.1007/978-1-4419-1145-2_4.
Changes in cell proliferation seen in cancers initiated by adenomatous polyposis coli (APC) gene mutation are driven by the loss of an ability to negatively regulate the canonical WNT signalling pathway. However, mutant APC proteins also lack the ability to interact with a number of other ligands and it is possible that the loss of these interactions could contribute to the phenotype or to the development ofcolorectal tumours. One such association is with the microtubule plus-end binding protein EB1. Originally identified as an APC binding partner, EB1 is now known to be part of an evolutionarily conserved family of proteins involved in the regulation of microtubule dynamics and microtubule-dependent processes. Roles for the interaction between APC and EB1 have been identified in cellular functions as diverse as directed cell migration and mitosis, with potentially important implications for the behaviour of both normal epithelial cells and colorectal cancer cells. In this chapter our current understanding of the functional role of the APC-EB1 interaction will be reviewed.
在由腺瘤性结肠息肉病(APC)基因突变引发的癌症中观察到的细胞增殖变化是由失去负调控经典 WNT 信号通路的能力驱动的。然而,突变型 APC 蛋白也缺乏与许多其他配体相互作用的能力,这些相互作用的丧失可能导致表型或结直肠肿瘤的发展。其中一种关联是与微管末端结合蛋白 EB1。EB1 最初被鉴定为 APC 的结合伙伴,现在已知它是参与微管动力学和微管依赖性过程调节的进化上保守的蛋白质家族的一部分。APC 和 EB1 之间的相互作用在细胞功能中具有多样化的作用,例如定向细胞迁移和有丝分裂,这对正常上皮细胞和结直肠癌细胞的行为都具有重要意义。在本章中,我们将回顾对 APC-EB1 相互作用的功能作用的当前理解。