The role of proliferation-associated protein 2G4 (PA2G4), alternatively known as ErbB3-binding protein 1 (EBP1), in cancer has become apparent over the past 20 years. PA2G4 expression levels are correlated with prognosis in a range of human cancers, including neuroblastoma, cervical, brain, breast, prostate, pancreatic, hepatocellular, and other tumors. There are two PA2G4 isoforms, PA2G4-p42 and PA2G4-p48, and although both isoforms of PA2G4 regulate cellular growth and differentiation, these isoforms often have opposing roles depending on the context. Therefore, PA2G4 can function either as a contextual tumor suppressor or as an oncogene, depending on the tissue being studied. However, it is unclear how distinct structural features of the two PA2G4 isoforms translate into different functional outcomes. In this review, we examine published structures to identify important structural and functional components of PA2G4 and consider how they may explain its crucial role in the malignant phenotype. We will highlight the lysine-rich regions, protein-protein interaction sites, and post-translational modifications of the two PA2G4 isoforms and relate these to the functional cellular role of PA2G4. These data will enable a better understanding of the function and structure relationship of the two PA2G4 isoforms and highlight the care that will need to be undertaken for those who wish to conduct isoform-specific structure-based drug design campaigns.

中文翻译：

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具有相反功能的PA2G4亚型在癌症中的结构图。

在过去的20年中，与增殖相关的蛋白2G4（PA2G4）（也称为ErbB3结合蛋白1（EBP1））在癌症中的作用变得显而易见。PA2G4表达水平与一系列人类癌症的预后相关，包括神经母细胞瘤，宫颈癌，脑癌，乳腺癌，前列腺癌，胰腺癌，肝细胞癌和其他肿瘤。有两种PA2G4亚型，PA2G4-p42和PA2G4-p48，尽管PA2G4的两种亚型都调节细胞的生长和分化，但根据环境的不同，这些亚型通常具有相反的作用。因此，取决于所研究的组织，PA2G4既可以用作背景肿瘤抑制剂，也可以用作癌基因。但是，尚不清楚两种PA2G4同工型的不同结构特征如何转化为不同的功能结果。在这篇评论中 我们研究了已发表的结构，以确定PA2G4的重要结构和功能组件，并考虑它们如何解释其在恶性表型中的关键作用。我们将突出显示两个PA2G4同工型的富含赖氨酸的区域，蛋白质-蛋白质相互作用位点和翻译后修饰，并将这些与PA2G4的功能性细胞作用相关。这些数据将使人们能够更好地理解这两种PA2G4同工型的功能和结构关系，并着重指出那些希望进行基于同工型特异性结构的药物设计活动的人们所需要进行的护理。蛋白质-蛋白质相互作用位点，以及两个PA2G4同工型的翻译后修饰，并将这些与PA2G4的功能性细胞作用相关。这些数据将使人们能够更好地理解这两种PA2G4同工型的功能和结构关系，并着重指出那些希望进行基于同工型特异性结构的药物设计活动的人们所需要进行的护理。蛋白质-蛋白质相互作用位点，以及两个PA2G4同工型的翻译后修饰，并将这些与PA2G4的功能性细胞作用相关。这些数据将使人们能够更好地理解这两种PA2G4同工型的功能和结构关系，并着重指出那些希望进行基于同工型特异性结构的药物设计活动的人们所需要进行的护理。