Department of Pharmacology, The Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19047, USA.
Cancer Metastasis Rev. 2018 Dec;37(4):665-676. doi: 10.1007/s10555-018-9764-7.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may represent the quintessential example of a moonlighting protein. The latter are a new, intriguing class of cell proteins which exhibit multiple activities in different subcellular locales apart from their initially, well-characterized function. As such, apart from its classical role in energy production, membrane-bound GAPDH is required for membrane fusion, endocytosis and, intriguingly, for iron transport. Cytoplasmic GAPDH regulates mRNA stability and is required for ER to Golgi trafficking. Nuclear GAPDH is involved in apoptosis, transcriptional gene regulation, the maintenance of DNA integrity, as well as nuclear tRNA export. Paradoxically, the etiology of a number of human pathologies is dependent upon GAPDH structure and function. In particular, recent evidence indicates a significant role for moonlighting GAPDH in tumorigenesis. Specifically, these include its role in the survival of tumor cells, in tumor angiogenesis, as well as its control of tumor cell gene expression and posttranscriptional regulation of tumor cell mRNA. Each of these activities correlates with increased tumor progression and, unfortunately, a poor prognosis for the afflicted individual.
甘油醛-3-磷酸脱氢酶（GAPDH）可能是具有多重功能蛋白质（moonlighting protein）的典型范例。后者是一类新的、有趣的细胞蛋白质，除了其最初的、特征明确的功能外，还在不同的亚细胞位置表现出多种活性。因此，除了其在能量产生中的经典作用外，膜结合的 GAPDH 还需要用于膜融合、内吞作用，并且有趣的是，还需要用于铁运输。细胞质 GAPDH 调节 mRNA 稳定性，并需要内质网到高尔基体的运输。核 GAPDH 参与细胞凋亡、转录基因调控、DNA 完整性的维持以及核 tRNA 输出。矛盾的是，许多人类病理学的病因取决于 GAPDH 的结构和功能。特别是，最近的证据表明，具有多重功能的 GAPDH 在肿瘤发生中具有重要作用。具体而言，这些作用包括其在肿瘤细胞存活、肿瘤血管生成中的作用，以及其对肿瘤细胞基因表达的控制和肿瘤细胞 mRNA 的转录后调控。这些活性都与肿瘤的进展增加相关，并且不幸的是，这会对受影响的个体产生不良预后。
