Department of Biochemistry and Molecular Biology and Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD 21201, USA.
Front Biosci (Landmark Ed). 2011 Jun 1;16(6):2307-25. doi: 10.2741/3855.
The mRNA-binding protein AUF1 regulates the expression of many key players in cancer including proto-oncogenes, regulators of apoptosis and the cell cycle, and pro-inflammatory cytokines, principally by directing the decay kinetics of their encoded mRNAs. Most studies support an mRNA-destabilizing role for AUF1, although other findings suggest additional functions for this factor. In this review, we explore how changes in AUF1 isoform distribution, subcellular localization, and post-translational protein modifications can influence the metabolism of targeted mRNAs. However, several lines of evidence also support a role for AUF1 in the initiation and/or development of cancer. Many AUF1-targeted transcripts encode products that control pro- and anti-oncogenic processes. Also, overexpression of AUF1 enhances tumorigenesis in murine models, and AUF1 levels are enhanced in some tumors. Finally, signaling cascades that modulate AUF1 function are deregulated in some cancerous tissues. Together, these features suggest that AUF1 may play a prominent role in regulating the expression of many genes that can contribute to tumorigenic phenotypes, and that this post-transcriptional regulatory control point may be subverted by diverse mechanisms in neoplasia.
mRNA 结合蛋白 AUF1 调节许多癌症关键因子的表达，包括原癌基因、凋亡和细胞周期调节剂以及促炎细胞因子，主要通过指导其编码 mRNA 的衰减动力学。大多数研究支持 AUF1 具有 mRNA 稳定作用，尽管其他研究结果表明该因子具有其他功能。在这篇综述中，我们探讨了 AUF1 同工型分布、亚细胞定位和翻译后蛋白修饰的变化如何影响靶 mRNA 的代谢。然而，有几条证据也支持 AUF1 在癌症的发生和/或发展中的作用。许多 AUF1 靶向的转录本编码控制原癌和抗癌过程的产物。此外，AUF1 的过表达增强了小鼠模型中的肿瘤发生，并且在一些肿瘤中 AUF1 的水平增强。最后，调节 AUF1 功能的信号级联在一些癌组织中失调。综上所述，这些特征表明 AUF1 可能在调节许多基因的表达中发挥重要作用，这些基因可能有助于肿瘤表型，并且这个转录后调控控制点可能在肿瘤发生中通过多种机制被颠覆。
