Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae.

A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB‐like sites in the A.gambiae Defensin and the Drosophila Diptericin and Cecropin promoters is also induced in larval nuclear extracts following infection. Gambif1 has the ability to bind to kappaB‐like sites in vitro. Co‐transfection assays in Drosophila mbn‐2 cells show that Gambif1 can activate transcription by interacting with the Drosophila Diptericin regulatory elements, but is not functionally equivalent to Dorsal in this assay. Gambif1 protein translocation to the nucleus and the appearance of kappaB‐like DNA binding activity can serve as molecular markers of activation of the immune system and open up the possibility of studying the role of defence reactions in determining mosquito susceptibility/refractoriness to malaria infection.

[1]  B. Thisse,et al.  Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product , 1991, Cell.

[2]  S. Harrison,et al.  Structure of the NF-kappa B p50 homodimer bound to DNA. , 1995, Nature.

[3]  M. Frasch,et al.  Maternal regulation of zerknüllt: a homoeobox gene controlling differentiation of dorsal tissues in Drosophila , 1987, Nature.

[4]  D. Baltimore,et al.  Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. , 1990, Nature.

[5]  C. Nüsslein-Volhard,et al.  cactus, a gene involved in dorsoventral pattern formation of Drosophila, is related to the IκB gene family of vertebrates , 1992, Cell.

[6]  M. Meister,et al.  Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila. , 1993, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[7]  D. Hultmark,et al.  kappa B-like motifs regulate the induction of immune genes in Drosophila. , 1993, Journal of molecular biology.

[8]  Y. Ip,et al.  The dorsal‐related immunity factor, Dif, is a sequence‐specific trans‐activator of Drosophila Cecropin gene expression. , 1995, The EMBO journal.

[9]  F. Kafatos,et al.  Inducible immune factors of the vector mosquito Anopheles gambiae: biochemical purification of a defensin antibacterial peptide and molecular cloning of preprodefensin cDNA , 1996, Insect molecular biology.

[10]  S. Sun,et al.  Cecropia immunoresponsive factor, an insect immunoresponsive factor with DNA-binding properties similar to nuclear-factor kappa B. , 1992, European journal of biochemistry.

[11]  P B Sigler,et al.  Structure of NF-kappa B p50 homodimer bound to a kappa B site. , 1995, Nature.

[12]  D. Hultmark,et al.  Immune reactions in Drosophila and other insects: a model for innate immunity. , 1993, Trends in genetics : TIG.

[13]  F. Weih,et al.  Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/Rel family , 1995, Cell.

[14]  P. Georgel,et al.  Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter. , 1995, Nucleic acids research.

[15]  G. Nolan,et al.  Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. , 1990, Cell.

[16]  M. Meister,et al.  Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements. , 1993, Biochemical and biophysical research communications.

[17]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[18]  N. Gay,et al.  Drosophila Toll and IL-1 receptor , 1991, Nature.

[19]  D. Baltimore,et al.  NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. , 1989, Cell.

[20]  J. Kuriyan,et al.  Structure of the NF-kappa B transcription factor: a holistic interaction with DNA. , 1995, Structure.

[21]  A. Israël,et al.  The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product , 1990, Cell.

[22]  R. Steward,et al.  Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. , 1995, The EMBO journal.

[23]  G. Nolan,et al.  DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. , 1991, Cell.

[24]  B. Franza,et al.  The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV , 1988, Cell.

[25]  A. Hinnebusch,et al.  A quantitative model for translational control of the GCN4 gene of Saccharomyces cerevisiae. , 1991, The New biologist.

[26]  B. M. Christensen,et al.  Insect immunity: isolation of three novel inducible antibacterial defensins from the vector mosquito, Aedes aegypti. , 1995, Insect biochemistry and molecular biology.

[27]  M. Meister,et al.  Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter. , 1994, The EMBO journal.

[28]  M. Levine,et al.  Dif, a dorsal-related gene that mediates an immune response in Drosophila , 1993, Cell.

[29]  F. Gannon,et al.  A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. , 1994, BioTechniques.

[30]  R. Steward.  Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. , 1987, Science.

[31]  R. Steward.  Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function , 1989, Cell.

[32]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[33]  M. Meister,et al.  A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Baltimore,et al.  Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. , 1995, Nature.

[35]  L. Possani,et al.  Effect of a cecropin-like synthetic peptide (Shiva-3) on the sporogonic development of Plasmodium berghei. , 1995, Experimental parasitology.

[36]  M. Meister,et al.  Insect immunity. Two 17 bp repeats nesting a kappa B‐related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria‐challenged Drosophila. , 1993, The EMBO journal.

[37]  R. Chalk,et al.  Purification of an insect defensin from the mosquito, Aedes aegypti. , 1994, Insect biochemistry and molecular biology.

[38]  R. Tjian,et al.  Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. , 1989, Science.

[39]  F. Collins,et al.  Sequence of a cDNA from the mosquito Anopheles gambiae encoding a homologue of human ribosomal protein S7. , 1993, Nucleic acids research.

[40]  P. Dunn.  BIOCHEMICAL ASPECTS OF INSECT IMMUNOLOGY , 1986 .

[41]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[42]  D. Kaslow,et al.  Effects of magainins and cecropins on the sporogonic development of malaria parasites in mosquitoes , 1989, Infection and immunity.

[43]  G. Franzoso,et al.  Structure, regulation and function of NF-kappa B. , 1994, Annual review of cell biology.

[44]  M. Siekevitz,et al.  Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. , 1989, Science.

[45]  J. Hoffmann,et al.  Innate immunity of insects. , 1995, Current opinion in immunology.

[46]  W. Trager.  Cell size in relation to the growth and metamorphosis of the mosquito, Aedes aegypti , 1937 .