Distinct Induction Patterns and Functions of Two Closely Related Interferon-inducible Human Genes, ISG54 and ISG56*

Human P54 and P56 proteins are tetratricopeptide proteins that are encoded by two closely related genes, ISG54 and ISG56. These genes are induced strongly but transiently when cells are treated with interferons or double-stranded RNA or infected with a variety of viruses. We observed that, although double-stranded RNA or Sendai virus infection induced the two genes with similar kinetics, their induction kinetics in response to interferon-β were quite different. The induction kinetics by virus infection were also different between two cell lines. Functionally the two proteins were similar. Like P56, P54 bound to the translation initiation factor eIF3 and inhibited translation. However, unlike P56, P54 bound to both the “e” and the “c” subunits of eIF3. Consequently, P54 inhibited two functions of eIF3. Like P56, it inhibited the ability of eIF3 to stabilize the eIF2·GTP·Met-tRNAi ternary complex. But in addition, it also inhibited the formation of the 48 S pre-initiation complex between the 40 S ribosomal subunit and the 20 S complex composed of eIF3, ternary complex, eIF4F, and mRNA. Thus, although similar in structure, the human P54 and P56 proteins are induced differently and function differently.

[1]  A. Shahangian,et al.  Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response , 2006, Nature.

[2]  Jun Huang,et al.  SIKE is an IKKε/TBK1‐associated suppressor of TLR3‐ and virus‐triggered IRF‐3 activation pathways , 2005 .

[3]  Osamu Takeuchi,et al.  IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction , 2005, Nature Immunology.

[4]  G. Sen,et al.  Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54. , 2005, Virology.

[5]  C. Coban,et al.  Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction , 2005, The Journal of experimental medicine.

[6]  W. Merrick,et al.  Mouse p56 Blocks a Distinct Function of Eukaryotic Initiation Factor 3 in Translation Initiation* , 2005, Journal of Biological Chemistry.

[7]  S. Goodbourn,et al.  The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Sakamoto,et al.  Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling , 2004, Nature Structural &Molecular Biology.

[9]  G. Sen,et al.  Novel functions of proteins encoded by viral stress-inducible genes. , 2004, Pharmacology & therapeutics.

[10]  Shizuo Akira,et al.  The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses , 2004, Nature Immunology.

[11]  Anton J. Enright,et al.  References and Notes Materials and Methods Som Text Figs. S1 to S9 Tables S1 to S3 References and Notes Protein Displacement by Dexh/d " Rna Helicases " without Duplex Unwinding , 2022 .

[12]  Akiko Iwasaki,et al.  Recognition of single-stranded RNA viruses by Toll-like receptor 7. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Akira,et al.  Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8 , 2004, Science.

[14]  T. Maniatis,et al.  IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  W. Merrick,et al.  Viral Stress-inducible Protein p56 Inhibits Translation by Blocking the Interaction of eIF3 with the Ternary Complex eIF2·GTP·Met-tRNAi* , 2003, Journal of Biological Chemistry.

[16]  F. Weih,et al.  NFκB Controls the Balance between Fas and Tumor Necrosis Factor Cell Death Pathways during T Cell Receptor-induced Apoptosis Via the Expression of Its Target Gene A20* , 2003, Journal of Biological Chemistry.

[17]  Roger E Bumgarner,et al.  Gene Expression Profiling of the Cellular Transcriptional Network Regulated by Alpha/Beta Interferon and Its Partial Attenuation by the Hepatitis C Virus Nonstructural 5A Protein , 2003, Journal of Virology.

[18]  Guo-Ping Zhou,et al.  Triggering the Interferon Antiviral Response Through an IKK-Related Pathway , 2003, Science.

[19]  T. Maniatis,et al.  IKKε and TBK1 are essential components of the IRF3 signaling pathway , 2003, Nature Immunology.

[20]  J. Hiscott,et al.  Multiple signaling pathways leading to the activation of interferon regulatory factor 3. , 2002, Biochemical pharmacology.

[21]  J. Darnell,et al.  Signalling: STATs: transcriptional control and biological impact , 2002, Nature Reviews Molecular Cell Biology.

[22]  G. Stark,et al.  IRF-3-dependent, NFκB- and JNK-independent activation of the 561 and IFN-β genes in response to double-stranded RNA , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Flavell,et al.  Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 , 2001, Nature.

[24]  Roger E Bumgarner,et al.  A Comprehensive View of Regulation of Gene Expression by Double-stranded RNA-mediated Cell Signaling* , 2001, The Journal of Biological Chemistry.

[25]  K. Hofmann,et al.  PCI complexes: pretty complex interactions in diverse signaling pathways. , 2001, Trends in plant science.

[26]  A. Goryachev,et al.  Herpes Simplex Virus Triggers and Then Disarms a Host Antiviral Response , 2001, Journal of Virology.

[27]  W. Merrick,et al.  A new pathway of translational regulation mediated by eukaryotic initiation factor 3 , 2000, The EMBO journal.

[28]  T. Taniguchi,et al.  Distinct and Essential Roles of Transcription Factors IRF-3 and IRF-7 in Response to Viruses for IFN-α/β Gene Induction , 2000 .

[29]  G. Sen,et al.  Induction of the human protein P56 by interferon, double-stranded RNA, or virus infection. , 2000, Virology.

[30]  Kathleen A. Boyle,et al.  Engagement of the Cellular Receptor for Glycoprotein B of Human Cytomegalovirus Activates the Interferon-Responsive Pathway , 1999, Molecular and Cellular Biology.

[31]  B. Williams,et al.  Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays , 1998 .

[32]  J. Whisstock,et al.  IFI60/ISG60/IFIT4, a new member of the human IFI54/IFIT2 family of interferon-stimulated genes. , 1998, Genomics.

[33]  G. Stark,et al.  How cells respond to interferons. , 1998, Annual review of biochemistry.

[34]  P Bucher,et al.  The PCI domain: a common theme in three multiprotein complexes. , 1998, Trends in biochemical sciences.

[35]  J W Hershey,et al.  Structure of cDNAs Encoding Human Eukaryotic Initiation Factor 3 Subunits , 1997, The Journal of Biological Chemistry.

[36]  G. Sen,et al.  Restoration of interferon responses of adenovirus E1A-expressing HT1080 cell lines by overexpression of p48 protein , 1997, Journal of virology.

[37]  G. Sen,et al.  Effects of adenovirus E1A protein on interferon-signaling. , 1996, Virology.

[38]  V. M. Pain.  Initiation of protein synthesis in eukaryotic cells. , 1996, European journal of biochemistry.

[39]  G. Stark,et al.  Transcriptional Induction by Double-stranded RNA Is Mediated by Interferon-stimulated Response Elements without Activation of Interferon-stimulated Gene Factor 3 (*) , 1995, The Journal of Biological Chemistry.

[40]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[41]  Mark S. Boguski,et al.  A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis , 1990, Cell.

[42]  D. Peretz,et al.  Enhancer‐like interferon responsive sequences of the human and murine (2′‐5′) oligoadenylate synthetase gene promoters. , 1988, The EMBO journal.

[43]  G. Stark,et al.  Interferon response element of the human gene 6‐16. , 1988, The EMBO journal.

[44]  J. Darnell,et al.  Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Darnell,et al.  Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[46]  G. Huez,et al.  Molecular cloning, full-length sequence and preliminary characterization of a 56-kDa protein induced by human interferons. , 1986, European journal of biochemistry.

[47]  M. Morgan,et al.  New initiation factor activity required for globin mRNA translation. , 1983, The Journal of biological chemistry.

[48]  B. Safer,et al.  Binding and release of radiolabeled eukaryotic initiation factors 2 and 3 during 80 S initiation complex formation. , 1979, The Journal of biological chemistry.

[49]  R. Benne,et al.  Purification and characterization of initiation factor IF-E3 from rabbit reticulocytes. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[50]  W. Anderson,et al.  A ribosome dissociation factor from rabbit reticulocytes distinct from initiation factor M3. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[51]  N. Sonenberg,et al.  Translational control of gene expression , 2000 .

[52]  W. Merrick.  Purification of protein synthesis initiation factors from rabbit reticulocytes. , 1979, Methods in enzymology.