Barbar Elisar
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
Biochemistry. 2008 Jan 15;47(2):503-8. doi: 10.1021/bi701995m. Epub 2007 Dec 20.
The operations within a living cell depend on the collective activity of networks of proteins, sometimes termed "interactomes". Within these networks, most proteins interact with few partners, while a small proportion of proteins, called hubs, participate in a large number of interactions and play a central role in organizing these interactomes. LC8 was first discovered as an essential component of the microtubule-based molecular motor dynein and as such is involved in fundamental processes, including retrograde vesicular trafficking, ciliary/flagellar motility, and cell division. More recently, evidence has accumulated that LC8 also interacts with proteins that are not clearly connected with dynein or microtubule-based transport, including some with roles in apoptosis, viral pathogenesis, enzyme regulation, and kidney development. Here, we introduce the idea that LC8 is a hub protein essential in diverse protein networks, and its function as a dynein light chain is but one of many. We further propose that the crucial regulatory roles of LC8 in various systems are due to its ability to promote dimerization of partially disordered proteins.
活细胞内的各种活动依赖于蛋白质网络的集体活动,这些网络有时被称为“相互作用组”。在这些网络中,大多数蛋白质只与少数几个伙伴相互作用,而一小部分被称为“枢纽”的蛋白质则参与大量的相互作用,并在组织这些相互作用组中发挥核心作用。LC8最初被发现是基于微管的分子马达动力蛋白的一个重要组成部分,因此参与了包括逆行囊泡运输、纤毛/鞭毛运动和细胞分裂在内的基本过程。最近,越来越多的证据表明,LC8还与一些与动力蛋白或基于微管的运输没有明显联系的蛋白质相互作用,包括一些在细胞凋亡、病毒发病机制、酶调节和肾脏发育中起作用的蛋白质。在这里,我们提出这样一种观点,即LC8是多种蛋白质网络中必不可少的枢纽蛋白,其作为动力蛋白轻链的功能只是众多功能之一。我们进一步提出,LC8在各种系统中的关键调节作用是由于它能够促进部分无序蛋白质的二聚化。