Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

Oncogene. 2004 Mar 4;23(9):1789-800. doi: 10.1038/sj.onc.1207300.


Melanoma differentiation associated gene-5 (mda-5) was identified by subtraction hybridization as a novel upregulated gene in HO-1 human melanoma cells induced to terminally differentiate by treatment with IFN-beta+MEZ. Considering its unique structure, consisting of a caspase recruitment domain (CARD) and an RNA helicase domain, it was hypothesized that mda-5 contributes to apoptosis occurring during terminal differentiation. We have currently examined the expression pattern of mda-5 in normal tissues, during induction of terminal differentiation and after treatment with type I IFNs. In addition, we have defined its genomic structure and chromosomal location. IFN-beta, a type I IFN, induces mda-5 expression in a biphasic and dose-dependent manner. Based on its temporal kinetics of induction and lack of requirement for prior protein synthesis mda-5 is an early type I IFN-responsive gene. The level of mda-5 mRNA is in low abundance in normal tissues, whereas expression is induced in a spectrum of normal and cancer cells by IFN-beta. Expression of mda-5 by means of a replication incompetent adenovirus, Ad.mda-5, induces apoptosis in HO-1 cells as confirmed by morphologic, biochemical and molecular assays. Additionally, the combination of Ad.mda-5+MEZ further augments apoptosis as observed in Ad.null or uninfected HO-1 cells induced to terminally differentiate by treatment with IFN-beta+MEZ. The mda-5 gene is located on human chromosome 2q24 and consists of 16 exons, without pseudogenes, and is conserved in the mouse genome. Present data documents that mda-5 is a novel type I IFN-inducible gene, which may contribute to apoptosis induction during terminal differentiation and during IFN treatment. The conserved genomic and protein structure of mda-5 in human and mouse will permit analysis of the evolution and developmental aspects of this gene.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Differentiation / drug effects
  • Cell Division
  • Cell Line, Tumor
  • Cell Survival
  • Chromosomes, Human, Pair 2 / genetics
  • DEAD-box RNA Helicases
  • Enzyme Induction / drug effects
  • Exons / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Genomics
  • Humans
  • Interferon Type I / pharmacology*
  • Interferon-Induced Helicase, IFIH1
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Protein Structure, Tertiary
  • RNA Helicases / chemistry
  • RNA Helicases / genetics*
  • RNA Helicases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Deletion / genetics
  • Signal Transduction / drug effects


  • Interferon Type I
  • RNA, Messenger
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases