GβL regulates TNFα-induced NF-k{cyrillic}B signaling by directly inhibiting the activation of Ik{cyrillic}B kinase

You Lim Kim, Jeong Eun Kim, Kum Joo Shin, Sukmook Lee, Curie Ahn, Junho Chung, Do Hyung Kim, Jae Young Seong, Jong-Ik Hwang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The transcriptional activation of NF-k{cyrillic}B, a critical player in both physiological and pathological cellular responses to diverse cytokines, is dependent on IKK activation. Although molecular mechanisms underlying IKK activation have been well elucidated, the processes that negatively regulate IKK activity are still largely unknown. Using yeast two-hybrid screening, we have identified GβL as an interacting partner of IKKβ. In this study, we demonstrate that GβL interacts with IKKα and IKKβ in vitro and in vivo. The C-terminal WD domains of GβL are required for the interaction with both the kinase domain and leucine zipper domain of IKKβ. Overexpression of GβL inhibits TNFα-induced activation of NF-k{cyrillic}B signaling, while down-regulation of GβL expression by small interfering RNA enhances NF-k{cyrillic}B activity. GβL constitutively interacts with IKKβ, and this interaction is enhanced by TNFα treatment. GβL also inhibits TNFα-induced phosphorylation of IKKs. Taken together, these data suggest that GβL is involved in the negative regulation of TNFα-stimulated NF-k{cyrillic}B signaling through a direct interaction with IKK.

Original languageEnglish
Pages (from-to)2127-2133
Number of pages7
JournalCellular Signalling
Volume20
Issue number11
DOIs
Publication statusPublished - 2008 Nov 1

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Leucine Zippers
Small Interfering RNA
Transcriptional Activation
Phosphotransferases
Down-Regulation
Yeasts
Phosphorylation
Cytokines
In Vitro Techniques

Keywords

  • GβL
  • IKK
  • NF-k{cyrillic}B signaling
  • TNFα

ASJC Scopus subject areas

  • Cell Biology

Cite this

GβL regulates TNFα-induced NF-k{cyrillic}B signaling by directly inhibiting the activation of Ik{cyrillic}B kinase. / Kim, You Lim; Kim, Jeong Eun; Shin, Kum Joo; Lee, Sukmook; Ahn, Curie; Chung, Junho; Kim, Do Hyung; Seong, Jae Young; Hwang, Jong-Ik.

In: Cellular Signalling, Vol. 20, No. 11, 01.11.2008, p. 2127-2133.

Research output: Contribution to journalArticle

Kim, You Lim ; Kim, Jeong Eun ; Shin, Kum Joo ; Lee, Sukmook ; Ahn, Curie ; Chung, Junho ; Kim, Do Hyung ; Seong, Jae Young ; Hwang, Jong-Ik. / GβL regulates TNFα-induced NF-k{cyrillic}B signaling by directly inhibiting the activation of Ik{cyrillic}B kinase. In: Cellular Signalling. 2008 ; Vol. 20, No. 11. pp. 2127-2133.
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