Exogenous signal-independent nuclear IκB kinase activation triggered by Nkx3.2 enables constitutive nuclear degradation of IκB-α in chondrocytes

Yeryoung Yong, Seung Won Choi, Hye Jeong Choi, Hyung Wook Nam, Jeong Ah Kim, Da Un Jeong, Don Young Kim, Yu Sam Kim, Dae-Won Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

NF-κB is a multifunctional transcription factor involved in diverse biological processes. It has been well documented that NF-κB can be activated in response to various stimuli. While signal-inducible NF-κB activation mechanisms have been extensively characterized, exogenous signal-independent intrinsic NF-κB activation processes remain poorly understood. Here we show that IκB kinase β (IKKβ) can be intrinsically activated in the nucleus by a homeobox protein termed Nkx3.2 in the absence of exogenous IKK-activating signals. We found that ubiquitin chain-dependent, but persistent, interactions between Nkx3.2 and NEMO (also known as IKKγ) can give rise to constitutive IKKβ activation in the nucleus. Once the Nkx3.2-NEMOIKK β complex is formed in the nucleus, IKKβ-induced Nkx3.2 phosphorylation at Ser148 and Ser168 allows βTrCP to be engaged to cause IκB-α ubiquitination independent of IκB-α phosphorylation at Ser32 and Ser36. Taken together, our results provide a novel molecular explanation as to how an intracellular factor such as Nkx3.2 can accomplish persistent nuclear IKK activation to enable intrinsic and constitutive degradation of IκB in the nucleus in the absence of exogenous NF-κB-activating signals, which, in turn, plays a role in chondrocyte viability maintenance.

Original languageEnglish
Pages (from-to)2802-2816
Number of pages15
JournalMolecular and Cellular Biology
Volume31
Issue number14
DOIs
Publication statusPublished - 2011 Jul 1

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Chondrocytes
Phosphotransferases
Phosphorylation
Biological Phenomena
Homeodomain Proteins
Ubiquitination
Ubiquitin
Transcription Factors
Maintenance

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Yong, Yeryoung ; Choi, Seung Won ; Choi, Hye Jeong ; Nam, Hyung Wook ; Kim, Jeong Ah ; Jeong, Da Un ; Kim, Don Young ; Kim, Yu Sam ; Kim, Dae-Won. / Exogenous signal-independent nuclear IκB kinase activation triggered by Nkx3.2 enables constitutive nuclear degradation of IκB-α in chondrocytes. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 14. pp. 2802-2816.
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Exogenous signal-independent nuclear IκB kinase activation triggered by Nkx3.2 enables constitutive nuclear degradation of IκB-α in chondrocytes. / Yong, Yeryoung; Choi, Seung Won; Choi, Hye Jeong; Nam, Hyung Wook; Kim, Jeong Ah; Jeong, Da Un; Kim, Don Young; Kim, Yu Sam; Kim, Dae-Won.

In: Molecular and Cellular Biology, Vol. 31, No. 14, 01.07.2011, p. 2802-2816.

Research output: Contribution to journalArticle

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AU - Yong, Yeryoung

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