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

• Tsuchiya, Yoshihiro

• Asano, Tomoichiro

• Nakayama, Keiko

• Kato, Tomohisa, Jr

• Karin, Michael

• Kamata, Hideaki

Abstract

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.

Journal

• Molecular Cell

  Molecular Cell 39 (4), 570-582, 2010-08-27

  Cell Press

Keywords

• SIGNALING
• CELLCYCLE
• PROTEINS

Details

• CRID: 1050296265985935488
• NII Article ID: 120002737833
• NII Book ID: AA1119005X
• Web Site: http://ir.lib.hiroshima-u.ac.jp/00030789
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles
  • KAKEN