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

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):637-42. doi: 10.1073/pnas.022637199.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Division
  • Cloning, Molecular
  • DEAD-box RNA Helicases
  • DNA, Complementary / genetics
  • Growth Inhibitors / metabolism
  • Humans
  • Interferon Type I / pharmacology
  • Interferon-Induced Helicase, IFIH1
  • Melanoma / enzymology*
  • Melanoma / genetics
  • Melanoma / pathology
  • Molecular Sequence Data
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA, Double-Stranded / metabolism
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay


  • DNA, Complementary
  • Growth Inhibitors
  • Interferon Type I
  • RNA, Double-Stranded
  • Recombinant Proteins
  • Adenosine Triphosphatases
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases

Associated data

  • GENBANK/AF095844