Open Access
Article
Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1
Beth E Zucconi1,Gerald M Wilson1
1
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
DOI: 10.2741/3855 Volume 16 Issue 6, pp.2307-2325
Published: 01 June 2011
(This article belongs to the Special Issue RNA binding proteins in disease)
Abstract

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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Beth E Zucconi, Gerald M Wilson. Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1. Frontiers in Bioscience-Landmark. 2011. 16(6); 2307-2325.