Regulation of ARE-mRNA Stability by Cellular Signaling: Implications for Human Cancer.
During recent years, it has become clear that regulation of mRNA stability is an important event in the control of gene expression. The stability of a large class of mammalian mRNAs is regulated by AU-rich elements (AREs) located in the mRNA 3' UTRs. mRNAs with AREs are inherently labile but as a response to different cellular cues they can become either stabilized, allowing expression of a given gene, or further destabilized to silence their expression. These tightly regulated mRNAs include many that encode growth factors, proto-oncogenes, cytokines, and cell cycle regulators. Failure to properly regulate their stability can therefore lead to uncontrolled expression of factors associated with cell proliferation and has been implicated in several human cancers. A number of transfactors that recognize AREs and regulate the translation and degradation of ARE-mRNAs have been identified. These transfactors are regulated by signal transduction pathways, which are often misregulated in cancers. This chapter focuses on the function of ARE-binding proteins with an emphasis on their regulation by signaling pathways and the implications for human cancer.
Department of Molecular Biology and Genetics, University of Aarhus, DK-8000, Aarhus C, Denmark.
Christian Kroun
CK
Damgaard
Jens
J
Lykke-Andersen
D000818:Animals; D006801:Humans; D009369:Neoplasms; D020871:RNA Stability; D012333:RNA, Messenger; D015398:Signal Transduction
D012333:RNA, Messenger