Brandon N J
Schizophrenia and Bipolar Research, Wyeth Discovery Neuroscience, CN8000, Princeton, NJ 08543, U.S.A.
Biochem Soc Trans. 2007 Nov;35(Pt 5):1283-6. doi: 10.1042/BST0351283.
Disrupted in schizophrenia 1 (DISC1) is emerging in the eyes of many as the most promising candidate of all the schizophrenia risk genes. This viewpoint is derived from the combination of genetic, clinical, imaging and rapidly advancing cell biology data around this gene. All of these areas have been reviewed extensively recently and this review will point you towards some of these excellent papers. My own personal view of the potential importance of DISC1 was echoed in a recent review which suggested that DISC1 may be a 'Rosetta Stone' for schizophrenia research [Ross, Margolis, Reading, Pletnikov and Coyle (2006) Neuron 52, 139-153]. Our own efforts to try to understand the function of DISC1 were through identification of its protein-binding partners. Through an extensive Y2H (yeast two-hybrid) and bioinformatics effort we generated the 'DISC1-Interactome', a comprehensive network of protein-protein interactions around DISC1. In two excellent industry-academia collaborations we focused on two main interacting partners: Ndel1 (nudE nuclear distribution gene E homologue-like 1), an enigmatic protein which may have diverse functions as both a cysteine protease and a key centrosomal structural protein; and PDE4B, a cAMP-specific phosphodiesterase. I will review the work around these two protein complexes in detail.
在许多人看来，精神分裂症1号基因（DISC1）是所有精神分裂症风险基因中最具潜力的候选基因。这一观点源于围绕该基因的遗传学、临床、影像学以及快速发展的细胞生物学数据的综合。最近，所有这些领域都已有广泛综述，本综述将为你指出其中一些优秀论文。最近一篇综述呼应了我个人对DISC1潜在重要性的看法，该综述表明DISC1可能是精神分裂症研究的“罗塞塔石碑”[罗斯、马戈利斯、雷丁、普列特尼科夫和科伊尔（2006年）《神经元》第52卷，第139 - 153页]。我们自己试图理解DISC1功能的努力是通过鉴定其蛋白质结合伙伴来进行的。通过广泛的酵母双杂交（Y2H）和生物信息学研究，我们构建了“DISC1相互作用组”，这是一个围绕DISC1的蛋白质 - 蛋白质相互作用的综合网络。在两项出色的产学研合作中，我们聚焦于两个主要的相互作用伙伴：Ndel1（nudE核分布基因E同源样蛋白1），一种神秘的蛋白质，它可能兼具半胱氨酸蛋白酶和关键中心体结构蛋白的多种功能；以及PDE4B，一种cAMP特异性磷酸二酯酶。我将详细回顾围绕这两种蛋白质复合物的研究工作。
