Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest 1117, Hungary.
Cells. 2020 Feb 4;9(2):357. doi: 10.3390/cells9020357.
The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeleton, including the microtubule network. Microtubules play crucial roles achieved by their decoration with proteins/enzymes as well as by posttranslational modifications. This review focuses on the Tubulin Polymerization Promoting Protein (TPPP/p25), a new microtubule associated protein, on its "regulatory functions by day and pathological functions at night". Physiologically, the moonlighting TPPP/p25 modulates the dynamics and stability of the microtubule network by bundling microtubules and enhancing the tubulin acetylation due to the inhibition of tubulin deacetylases. The optimal endogenous TPPP/p25 level is crucial for its physiological functions, to the differentiation of oligodendrocytes, which are the major constituents of the myelin sheath. Pathologically, TPPP/p25 forms toxic oligomers/aggregates with α-synuclein in neurons and oligodendrocytes in Parkinson's disease and Multiple System Atrophy, respectively; and their complex is a potential therapeutic drug target. TPPP/p25-derived microtubule hyperacetylation counteracts uncontrolled cell division. All these issues reveal the anti-mitotic and α-synuclein aggregation-promoting potency of TPPP/p25, consistent with the finding that Parkinson's disease patients have reduced risk for certain cancers.
真核细胞的感应、整合和协调功能是通过细胞骨架的复杂超微结构排列和多种功能实现的，包括微管网络。微管通过其与蛋白质/酶的装饰以及翻译后修饰发挥着至关重要的作用。本综述重点介绍了微管相关蛋白 Tubulin Polymerization Promoting Protein (TPPP/p25)，它是一种新的微管相关蛋白，具有“白天的调节功能和夜间的病理功能”。在生理上，多功能 TPPP/p25 通过捆绑微管和增强微管乙酰化来调节微管网络的动态和稳定性，这是由于抑制了微管去乙酰化酶。最佳的内源性 TPPP/p25 水平对于其生理功能至关重要，对于少突胶质细胞的分化也是如此，少突胶质细胞是髓鞘的主要成分。在病理上，TPPP/p25 在帕金森病和多系统萎缩症的神经元和少突胶质细胞中与α-突触核蛋白形成毒性寡聚物/聚集体；它们的复合物是潜在的治疗药物靶点。TPPP/p25 衍生的微管过度乙酰化可阻止不受控制的细胞分裂。所有这些问题都揭示了 TPPP/p25 的抗有丝分裂和α-突触核蛋白聚集促进作用，与帕金森病患者患某些癌症风险降低的发现一致。
