Ramesh Babu Polani B
Center for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Bharath Institute of Science and Technology, Selaiyur, Tambaram, Chennai, India.
J Genet Eng Biotechnol. 2023 Jul 19;21(1):78. doi: 10.1186/s43141-023-00531-8.
Tubulins are highly conserved globular proteins involved in stabilization of cellular cytoskeletal microtubules during cell cycle. Different isoforms of tubulins are differentially expressed in various cell types, and their protein-protein interactions (PPIs) analysis will help in identifying the anti-microtubular drug targets for cancer and neurological disorders. Numerous web-based PPIs analysis methods are recently being used, and in this paper, I used Gene Ontology (GO) tools, e.g., Stringbase, ProteomeHD, GeneMANIA, and ShinyGO, to identify anti-microtubular target proteins by selecting strongly interacting proteins of tubulins.
I used 6 different human tubulin isoforms (two from each of α-, β-, and γ-tubulin) and found several thousands of node-to-node protein interactions (highest 4956 in GeneMANIA) and selected top 10 strongly interacting node-to-node interactions with highest score, which included 7 tubulin family protein and 6 non-tubulin family proteins (total 13). Functional enrichment analysis indicated a significant role of these 13 proteins in nucleation, polymerization or depolymerization of microtubules, membrane tethering and docking, dorsal root ganglion development, mitotic cycle, and cytoskeletal organization. I found γ-tubulins (TUBG1, TUBGCP4, and TUBBGCP6) were known to contribute majorly for tubulin-associated functions followed by α-tubulin (TUBA1A) and β-tubulins (TUBB AND TUBB3). In PPI results, I found several non-tubular proteins interacting with tubulins, and six of them (HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41) were found closely associated with their functions.
Increasing number of regulatory proteins and subpopulation of tubulin proteins are being reported with poor understanding in their association with microtubule assembly and disassembly. The functional enrichment analysis of tubulin isoforms using recent GO tools resulted in identification of γ-tubulins playing a key role in microtubule functions and observed non-tubulin family of proteins HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41 strongly interacting functional proteins of tubulins. The present study yields a promising model system using GO tools to narrow down tubulin-associated proteins as a drug target in cancer, Alzheimer's, neurological disorders, etc.
微管蛋白是高度保守的球状蛋白，在细胞周期中参与细胞细胞骨架微管的稳定。微管蛋白的不同亚型在各种细胞类型中差异表达，对它们的蛋白质-蛋白质相互作用（PPI）进行分析将有助于确定针对癌症和神经疾病的抗微管药物靶点。最近，许多基于网络的PPI分析方法被广泛应用。在本文中，我使用了基因本体（GO）工具，如Stringbase、ProteomeHD、GeneMANIA和ShinyGO，通过选择与微管蛋白强烈相互作用的蛋白质来鉴定抗微管靶点蛋白。
我使用了6种不同的人类微管蛋白亚型（α-、β-和γ-微管蛋白各两种），发现了数千个节点到节点的蛋白质相互作用（GeneMANIA中最多为4956个），并选择了得分最高的前10个强烈相互作用的节点到节点相互作用，其中包括7种微管蛋白家族蛋白和6种非微管蛋白家族蛋白（共13种）。功能富集分析表明，这13种蛋白质在微管的成核、聚合或解聚、膜系留和对接、背根神经节发育、有丝分裂周期和细胞骨架组织中发挥着重要作用。我发现γ-微管蛋白（TUBG1、TUBGCP4和TUBBGCP6）在微管蛋白相关功能中起主要作用，其次是α-微管蛋白（TUBA1A）和β-微管蛋白（TUBB和TUBB3）。在PPI结果中，我发现有几种非微管蛋白与微管蛋白相互作用，其中六种（HTT、DPYSL2、SKI、UNC5C、NINL和DDX41）与它们的功能密切相关。
越来越多的调节蛋白和微管蛋白亚群被报道，但人们对它们与微管组装和解聚的关联了解甚少。使用最新的GO工具对微管蛋白亚型进行功能富集分析，结果表明γ-微管蛋白在微管功能中起关键作用，并且观察到非微管蛋白家族的蛋白质HTT、DPYSL2、SKI、UNC5C、NINL和DDX41是与微管蛋白强烈相互作用的功能蛋白。本研究利用GO工具产生了一个有前景的模型系统，可用于缩小微管蛋白相关蛋白作为癌症、阿尔茨海默病、神经疾病等药物靶点的范围。
