Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.
Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Cancers (Basel). 2014 Mar 25;6(2):663-83. doi: 10.3390/cancers6020663.
Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching-PRISM).
细胞因子是组织与免疫系统之间的通讯分子。它们在癌症的起始、促进、转移和免疫治疗中发挥着重要作用。细胞因子信号转导的结构途径包含了它们的相互作用，可以帮助我们理解它们在肿瘤微环境中的作用。在这里，我们的目的是从结构角度概述细胞因子在肿瘤发展中的作用。蛋白质-蛋白质相互作用的原子细节有助于理解上游信号是如何转导的；蛋白质的高级寡聚化模式如何影响其功能；突变、抑制剂或拮抗剂如何改变细胞后果；为什么相同的蛋白质会导致不同的结果，以及哪些替代的平行途径可以接管。它们还有助于设计针对蛋白质的新药/抑制剂，或者通过模拟干扰素-γ等天然拮抗剂来设计。由于结构数据库（PDB）有限，结构途径主要是由一系列预测的二元蛋白质-蛋白质相互作用构建的。下面，为了说明蛋白质-蛋白质相互作用如何帮助阐明细胞因子的作用，我们利用一种强大的算法（结构匹配的蛋白质相互作用预测-PRISM）来模拟一些细胞因子相互作用复合物。
