Nuclear IKKβ Is an Adaptor Protein for IκBα Ubiquitination and Degradation in UV-Induced NF-κB Activation

Yoshihiro Tsuchiya, Tomoichiro Asano, Keiko Nakayama, Tomohisa Kato, Michael Karin, Hideaki Kamata

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)


Proinflammatory cytokines activate NF-κB using the IκB kinase (IKK) complex that phosphorylates inhibitory proteins (IκBs) at N-terminal sites resulting in their ubiquitination and degradation in the cytoplasm. Although ultraviolet (UV) irradiation does not lead to IKK activity, it activates NF-κB by an unknown mechanism through IκBα degradation without N-terminal phosphorylation. Here, we describe an adaptor function of nuclear IKKβ in UV-induced IκBα degradation. UV irradiation induces the nuclear translocation of IκBα and association with IKKβ, which constitutively interacts with β-TrCP through heterogeneous ribonucleoprotein-U (hnRNP-U) leading to IκBα ubiquitination and degradation. Furthermore, casein kinase 2 (CK2) and p38 associate with IKKβ and promote IκBα degradation by phosphorylation at C-terminal sites. Thus, nuclear IKKβ acts as an adaptor protein for IκBα degradation in UV-induced NF-κB activation. NF-κB activated by the nuclear IKKβ adaptor protein suppresses anti-apoptotic gene expression and promotes UV-induced cell death.

Original languageEnglish
Pages (from-to)570-582
Number of pages13
JournalMolecular Cell
Issue number4
Publication statusPublished - 2010 Aug


  • Cellcycle
  • Proteins
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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