IFN-zeta/ limitin: a member of type I IFN with mild lympho-myelosuppression.
Interferon (IFN)-Zeta/limitin has been considered as a novel type I IFN by the Nomenclature Committee of the International Society for Interferon and Cytokine Research. IFN-Zeta/limitin shows some sequence homology with IFN-alpha and IFN-beta, has a globular structure with five alpha-helices and four loops, and recognizes IFN-alpha/beta receptor. Although IFN-zeta/limitin displays antiviral, immunomodulatory, and antitumor effects, it has much less lympho-myelosuppressive activities than IFN-alpha. Treatment of cells with type I IFNs induces and/or activates a number of molecules, which regulate cell cycle and apoptosis. It is noteworthy that IFN-zeta/limitin activates the Tyk2-Daxx and Tyk2-Crk pathways weaker than IFN-alpha. Because experiments using antisense oligonucleotides have revealed their essential role in type I IFN-related suppression of lympho-hematopoiesis, little ability of IFN-zeta/limitin to activate the Tyk2-dependent signaling pathway may explain its uniquely narrow range of biological activities. Further analysis of structure-function relationship of type I IFNs will establish an engineered cytokine with useful features of IFN-zeta/limitin.
Oritani
Kenji
K
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan. oritani@bldon.med.osaka-u.ac.jp
Kanakura
Yuzuru
Y
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D056970:Co-Repressor Proteins; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D019891:Leukopoiesis / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050737:Proto-Oncogene Proteins c-crk; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D016207:Cytokines; C106985:DAXX protein, human; C491473:Daxx protein, mouse; D007370:Interferon Type I; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; C410906:limitin