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beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha.

Publication ,  Journal Article
Witherow, DS; Garrison, TR; Miller, WE; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
June 8, 2004

In addition to their roles in desensitization and signaling of seven-membrane-spanning receptors, beta-arrestins have been more recently implicated in regulating non-seven-membrane-spanning receptor pathways. By using a yeast two-hybrid screen, we identified the inhibitor of NF-kappaB, IkappaBalpha, as a binding partner of beta-arrestin 1. Both beta-arrestin 1 and 2 interact with IkappaBalpha in transfected cells as assessed by immunoprecipitation experiments. Additionally, upstream kinases known to regulate the function of IkappaBalpha, such as IkappaB kinase alpha and beta and NF-kappaB-inducing kinase, were also shown to interact with beta-arrestin. Overexpression of either beta-arrestin 1 or beta-arrestin 2 led to marked inhibition of NF-kappaB activity, as measured by reporter gene activity. Inhibition of NF-kappaB activity was independent of the type of stimulus used for NF-kappaB activation. Conversely, suppression of beta-arrestin 1, but not beta-arrestin 2, expression by using RNA interference led to a 3-fold increase in tumor necrosis factor-stimulated NF-kappaB activity as measured by NF-kappaB mobility-shift analysis. These data uncover a role of beta-arrestins in the regulation of NF-kappaB-mediated gene regulation.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 8, 2004

Volume

101

Issue

23

Start / End Page

8603 / 8607

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Two-Hybrid System Techniques
  • Transfection
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • RNA Interference
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
 

Citation

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Witherow, D. S., Garrison, T. R., Miller, W. E., & Lefkowitz, R. J. (2004). beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci U S A, 101(23), 8603–8607. https://doi.org/10.1073/pnas.0402851101
Witherow, D Scott, Tiffany Runyan Garrison, William E. Miller, and Robert J. Lefkowitz. “beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha.Proc Natl Acad Sci U S A 101, no. 23 (June 8, 2004): 8603–7. https://doi.org/10.1073/pnas.0402851101.
Witherow DS, Garrison TR, Miller WE, Lefkowitz RJ. beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603–7.
Witherow, D. Scott, et al. “beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha.Proc Natl Acad Sci U S A, vol. 101, no. 23, June 2004, pp. 8603–07. Pubmed, doi:10.1073/pnas.0402851101.
Witherow DS, Garrison TR, Miller WE, Lefkowitz RJ. beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603–8607.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

June 8, 2004

Volume

101

Issue

23

Start / End Page

8603 / 8607

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Two-Hybrid System Techniques
  • Transfection
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • RNA Interference
  • NF-kappa B
  • NF-KappaB Inhibitor alpha