title: The small interferon-induced transmembrane genes and proteins.
abstract: Interferon-induced transmembrane (IFITM) genes are transcribed in most tissues and are with the exception of IFITM5 interferon inducible. They are involved in early development, cell adhesion, and control of cell growth. Most IFITM genes are activated in response to bacterial and viral infections, and the exact host immune defense mechanisms are still unknown. Elevated gene expression triggered by past or chronic inflammation could prevent spreading of pathogens by limiting host cell proliferation. Accordingly, induction in cells with low basal protein levels is sufficient to drive growth arrest and a senescence-like morphology. On the other hand, loss of IFITM levels in cancer is correlated with pronounced malignancy; thus, these genes are considered as tumor suppressors. However, several cancer cells have deregulated high levels of IFITM transcripts, indicating a tumor progression stage where at least one of the interferon-controlled antiproliferative pathways has been silenced. Phylogenetic analyses of the protein coding genomic sequences suggest a single interferon-inducible gene in the common ancestor of rodents and primates. Biological functions studied so far may have evolved in parallel, and functional characterization of IFITM proteins will provide insight into innate immune defense, cancer development, and other pathways.
authors.affiliation: Non-Clinical Safety, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Fredy
authors.initials: F
authors.lastname: Siegrist
authors.forename: Martin
authors.initials: M
authors.lastname: Ebeling
authors.forename: Ulrich
authors.initials: U
authors.lastname: Certa
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C062010:leu-13 antigen; D007372:Interferons