Cactus-independent nuclear translocation of Drosophila RELISH

Elizabeth A. Olmsted, Jeremy S. Blum, Donna Rill, Patricia Yotnda, Zbigniew Gugala, Ronald W. Lindsey Alan R Davis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Abstract Insects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production of antimicrobial peptides. Induction of these antimicrobial peptides in Drosophila has been well established to involve NF-κB elements. We present evidence here for a molecular mechanism of Lipopolysaccharide (LPS)-induced signaling involving Drosophila NF-κB, RELISH, in Drosophila S2 cells. We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C-terminal ankyrin-repeats from the N-terminal Rel homology domain (RHD). Examination of the cellular localization of RELISH reveals that the timing of this processing coincides with the nuclear translocation of the RHD and the retention of the ankyrin-repeats within the cytoplasm. Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin. Over-expression of the RHD but not full-length RELISH results in an increase in the promoter activity of the cecropin At gene in the absence of LPS. Furthermore, the LPS-induced expression of these antibacterial peptides is greatly reduced when RELISH expression is depleted via RNA-mediated interference. In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of cactus. Taken together, these results suggest that this signaling mechanism involving the processing of RELISH followed by nuclear translocation of the RHD is central to the induction of at least part of the antimicrobial response in Drosophila, and is largely independent of cactus regulation.

Original languageEnglish (US)
Pages (from-to)22-37
Number of pages16
JournalJournal of Cellular Biochemistry
Volume82
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Cactaceae
Drosophila
Lipopolysaccharides
Cecropins
Ankyrin Repeat
Peptides
Processing
RNA Interference
Genes
Terminal Repeat Sequences
Protein C
Innate Immunity
Insects
Cytoplasm
Chemical activation
RNA
Infection
Proteins

Keywords

  • /-κB
  • Antimicrobial peptides
  • Cactus
  • Innate immunity
  • NF-κB
  • RNA interference (RNAi)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Olmsted, E. A., Blum, J. S., Rill, D., Yotnda, P., Gugala, Z., & Lindsey Alan R Davis, R. W. (2001). Cactus-independent nuclear translocation of Drosophila RELISH. Journal of Cellular Biochemistry, 82(1), 22-37. https://doi.org/10.1002/jcb.1144

Cactus-independent nuclear translocation of Drosophila RELISH. / Olmsted, Elizabeth A.; Blum, Jeremy S.; Rill, Donna; Yotnda, Patricia; Gugala, Zbigniew; Lindsey Alan R Davis, Ronald W.

In: Journal of Cellular Biochemistry, Vol. 82, No. 1, 2001, p. 22-37.

Research output: Contribution to journalArticle

Olmsted, EA, Blum, JS, Rill, D, Yotnda, P, Gugala, Z & Lindsey Alan R Davis, RW 2001, 'Cactus-independent nuclear translocation of Drosophila RELISH', Journal of Cellular Biochemistry, vol. 82, no. 1, pp. 22-37. https://doi.org/10.1002/jcb.1144
Olmsted, Elizabeth A. ; Blum, Jeremy S. ; Rill, Donna ; Yotnda, Patricia ; Gugala, Zbigniew ; Lindsey Alan R Davis, Ronald W. / Cactus-independent nuclear translocation of Drosophila RELISH. In: Journal of Cellular Biochemistry. 2001 ; Vol. 82, No. 1. pp. 22-37.
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AB - Abstract Insects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production of antimicrobial peptides. Induction of these antimicrobial peptides in Drosophila has been well established to involve NF-κB elements. We present evidence here for a molecular mechanism of Lipopolysaccharide (LPS)-induced signaling involving Drosophila NF-κB, RELISH, in Drosophila S2 cells. We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C-terminal ankyrin-repeats from the N-terminal Rel homology domain (RHD). Examination of the cellular localization of RELISH reveals that the timing of this processing coincides with the nuclear translocation of the RHD and the retention of the ankyrin-repeats within the cytoplasm. Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin. Over-expression of the RHD but not full-length RELISH results in an increase in the promoter activity of the cecropin At gene in the absence of LPS. Furthermore, the LPS-induced expression of these antibacterial peptides is greatly reduced when RELISH expression is depleted via RNA-mediated interference. In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of cactus. Taken together, these results suggest that this signaling mechanism involving the processing of RELISH followed by nuclear translocation of the RHD is central to the induction of at least part of the antimicrobial response in Drosophila, and is largely independent of cactus regulation.

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