mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties.
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-5 is an early response gene inducible by IFN and tumor necrosis factor-alpha, responding predominantly to IFN-beta. Protein kinase C activation by mezerein further augments mda-5 expression induced by IFN-beta. Expression of mda-5 is controlled transcriptionally by IFN-beta, and the MDA-5 protein localizes in the cytoplasm. mda-5 displays RNA-dependent ATPase activity, and ectopic expression of mda-5 in human melanoma cells inhibits colony formation. In these contexts, mda-5 may 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.
Kang
Dong-chul
DC
Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Gopalkrishnan
Rahul V
RV
Wu
Qingping
Q
Jankowsky
Eckhard
E
Pyle
Anna Marie
AM
Fisher
Paul B
PB
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases; D018076:DNA, Complementary / Q000235:genetics; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D000072640:Interferon-Induced Helicase, IFIH1; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018076:DNA, Complementary; D006131:Growth Inhibitors; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases