Linked Life Data

14676839

Source:http://linkedlifedata.com/resource/pubmed/id/14676839

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-3-5
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1789-800
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14676839-Animals, pubmed-meshheading:14676839-Apoptosis, pubmed-meshheading:14676839-Cell Differentiation, pubmed-meshheading:14676839-Cell Division, pubmed-meshheading:14676839-Cell Line, Tumor, pubmed-meshheading:14676839-Cell Survival, pubmed-meshheading:14676839-Chromosomes, Human, Pair 2, pubmed-meshheading:14676839-DEAD-box RNA Helicases, pubmed-meshheading:14676839-Enzyme Induction, pubmed-meshheading:14676839-Exons, pubmed-meshheading:14676839-Gene Expression Profiling, pubmed-meshheading:14676839-Gene Expression Regulation, Enzymologic, pubmed-meshheading:14676839-Genomics, pubmed-meshheading:14676839-Humans, pubmed-meshheading:14676839-Interferon Type I, pubmed-meshheading:14676839-Melanoma, pubmed-meshheading:14676839-Mice, pubmed-meshheading:14676839-Protein Structure, Tertiary, pubmed-meshheading:14676839-RNA, Messenger, pubmed-meshheading:14676839-RNA Helicases, pubmed-meshheading:14676839-Sequence Deletion, pubmed-meshheading:14676839-Signal Transduction
pubmed:year
2004
pubmed:articleTitle
Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene.
pubmed:affiliation
Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't