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

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-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.

• Authors: Dong-chul Kang, Rahul V Gopalkrishnan, Qingping Wu, Eckhard Jankowsky, Anna Marie Pyle, Paul B Fisher
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 2 Pg. 637-42 (Jan 22 2002) ISSN: 0027-8424 [Print] United States
• PMID: 11805321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• Adenosine Triphosphatases (genetics, 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, genetics, pathology)
• Molecular Sequence Data
• RNA Helicases (genetics, metabolism)
• RNA, Double-Stranded (metabolism)
• Recombinant Proteins
• Sequence Homology, Amino Acid
• Tumor Cells, Cultured
• Tumor Stem Cell Assay