mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Human melanoma cells can be reprogrammed to terminally differentiate and irreversibly lose proliferative capacity by appropriate pharmacological manipulation. Subtraction hybridization identified melanoma differentiation-associated gene-5 (mda-5) as a gene induced during differentiation, cancer reversion, and programmed cell death (apoptosis). This gene contains both a caspase recruitment domain and putative DExH group RNA helicase domains. Atypical helicase motifs of MDA-5 deviate from consensus sequences but are well conserved in a potentially new group of cloned and hypothetical proteins.mda-5is an early response gene inducible by IFN and tumor necrosis factor-α, responding predominantly to IFN-β. Protein kinase C activation by mezerein further augments mda-5 expression induced by IFN-β. Expression ofmda-5is controlled transcriptionally by IFN-β, and the MDA-5 protein localizes in the cytoplasm.mda-5displays RNA-dependent ATPase activity, and ectopic expression ofmda-5in human melanoma cells inhibits colony formation. In these contexts,mda-5may function as a mediator of IFN-induced growth inhibition and/or apoptosis. MDA-5 is a double-stranded RNA-dependent ATPase that contains both a caspase recruitment domain and RNA helicase motifs, with a confirmed association with growth and differentiation in human melanoma cells.