Sharp Adam, Crabb Simon J, Townsend Paul A, Cutress Ramsey I, Brimmell Matthew, Wang Xiu-hong, Packham Graham
Cancer Research UK Oncology Unit, The Somers Cancer Research Building, University of Southampton School of Medicine, Southampton General Hospital, Southampton, S016 6YD, UK.
Expert Rev Mol Med. 2004 Mar 22;6(7):1-15. doi: 10.1017/S1462399404007537.
BAG-1 is a multifunctional protein that exists as several differentially localised and functionally distinct isoforms. BAG-1 isoforms interact with a diverse array of molecular targets and regulate a wide range of cellular processes, including proliferation, survival, transcription, apoptosis, metastasis and motility. The BAG domain of BAG-1 interacts with chaperone molecules and this is considered important for many BAG-1 functions. The ability of BAG-1 to regulate such a wide variety of cellular processes suggests it might play an important role in many cancer types. For example, regulation of nuclear hormone receptor function and susceptibility to apoptosis might have a major impact on cancer development, progression and response to therapy. There is also increasing evidence that BAG-1 expression is altered in a variety of human malignancies relative to normal cells, and with further understanding of BAG-1 function it might become a powerful prognostic/predictive marker in human cancer. This review describes the structure and function of BAG-1 isoforms and the potential clinical implications of their expression in tumour cells.
BAG-1是一种多功能蛋白质,以几种定位不同且功能各异的亚型形式存在。BAG-1亚型与多种分子靶点相互作用,并调节广泛的细胞过程,包括增殖、存活、转录、凋亡、转移和运动。BAG-1的BAG结构域与伴侣分子相互作用,这被认为对许多BAG-1功能很重要。BAG-1调节如此多种细胞过程的能力表明它可能在多种癌症类型中发挥重要作用。例如,核激素受体功能的调节和对凋亡的易感性可能对癌症的发展、进展和治疗反应产生重大影响。越来越多的证据表明,相对于正常细胞,BAG-1在多种人类恶性肿瘤中的表达发生了改变,随着对BAG-1功能的进一步了解,它可能成为人类癌症中一种强大的预后/预测标志物。这篇综述描述了BAG-1亚型的结构和功能及其在肿瘤细胞中表达的潜在临床意义。