4.5 Article

Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1

Journal

FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 16, Issue -, Pages 2307-2325

Publisher

FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/3855

Keywords

AUF1; alternative splicing; RNA turnover; RNA-Binding Protein; Phosphorylation; Cancer; Review

Funding

  1. NIH [R01 CA102428, T32 GM066706]

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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.

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