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Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes.

Publication ,  Journal Article
Diatchenko, L; Romanov, S; Malinina, I; Clarke, J; Tchivilev, I; Li, X; Makarov, SS
Published in: J Leukoc Biol
December 2005

The transcription factor nuclear factor (NF)-kappaB controls the expression of genes involved in inflammation, cell proliferation, apoptosis, and differentiation. Impaired regulation of NF-kappaB has been associated with many diseases; thus, there is significant interest in therapeutic approaches based on modulation of this transcription factor. NF-kappaB activity is controlled by numerous signaling molecules, many of which are potentially to be identified. Monocytes are principal effectors of the immune system, and monocyte adherence is the first step leading to their activation and differentiation. Adherence induces activation of NF-kappaB, resulting in the induction of proinflammatory genes as well as anti-inflammatory genes, which counterbalance and limit the intensity and duration of NF-kappaB activation. Here, to identify novel mediators of NF-kappaB signaling, we used the model of monocyte adherence to perform a systematic, genome-wide survey of adherence-induced genes. Having isolated mRNAs from nonadherent and adherent primary human monocytes, we constructed suppressive subtraction hybridization libraries containing cDNAs, which were differentially regulated by adherence. Of 366 identified differentially expressed genes, most were found to be up-regulated by adherence. Having analyzed a subset of these genes, we found that the library was enriched with inhibitors of NF-kappaB. Three of those (an orphan nuclear receptor NUR77, a guanosine 5'-diphosphate/guanosine 5'-triphosphate exchange factor RABEX5, and a PRK1-associated protein AWP1) were particularly potent inhibitors of NF-kappaB activation. Thus, the collection of monocyte adherence-regulated genes represents a rich source for the identification of novel components of the machinery that controls NF-kappaB activation.

Duke Scholars

Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

December 2005

Volume

78

Issue

6

Start / End Page

1366 / 1377

Location

England

Related Subject Headings

  • Up-Regulation
  • Transcription Factors
  • Signal Transduction
  • Receptors, Steroid
  • Receptors, Cytoplasmic and Nuclear
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • NF-kappa B
  • Monocytes
  • Inflammation
  • Immunology
 

Citation

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ICMJE
MLA
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Diatchenko, L., Romanov, S., Malinina, I., Clarke, J., Tchivilev, I., Li, X., & Makarov, S. S. (2005). Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes. J Leukoc Biol, 78(6), 1366–1377. https://doi.org/10.1189/jlb.0405211
Diatchenko, Luda, Sergei Romanov, Inga Malinina, Julie Clarke, Igor Tchivilev, Xiangli Li, and Sergei S. Makarov. “Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes.J Leukoc Biol 78, no. 6 (December 2005): 1366–77. https://doi.org/10.1189/jlb.0405211.
Diatchenko L, Romanov S, Malinina I, Clarke J, Tchivilev I, Li X, et al. Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes. J Leukoc Biol. 2005 Dec;78(6):1366–77.
Diatchenko, Luda, et al. “Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes.J Leukoc Biol, vol. 78, no. 6, Dec. 2005, pp. 1366–77. Pubmed, doi:10.1189/jlb.0405211.
Diatchenko L, Romanov S, Malinina I, Clarke J, Tchivilev I, Li X, Makarov SS. Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes. J Leukoc Biol. 2005 Dec;78(6):1366–1377.

Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

December 2005

Volume

78

Issue

6

Start / End Page

1366 / 1377

Location

England

Related Subject Headings

  • Up-Regulation
  • Transcription Factors
  • Signal Transduction
  • Receptors, Steroid
  • Receptors, Cytoplasmic and Nuclear
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • NF-kappa B
  • Monocytes
  • Inflammation
  • Immunology