Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation.
Proinflammatory cytokines activate NF-kappaB using the IkappaB kinase (IKK) complex that phosphorylates inhibitory proteins (IkappaBs) 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-kappaB by an unknown mechanism through IkappaBalpha degradation without N-terminal phosphorylation. ... Here, we describe an adaptor function of nuclear IKKbeta in UV-induced IkappaBalpha degradation. UV irradiation induces the nuclear translocation of IkappaBalpha and association with IKKbeta, which constitutively interacts with beta-TrCP through heterogeneous ribonucleoprotein-U (hnRNP-U) leading to IkappaBalpha ubiquitination and degradation. Furthermore, casein kinase 2 (CK2) and p38 associate with IKKbeta and promote IkappaBalpha degradation by phosphorylation at C-terminal sites. Thus, nuclear IKKbeta acts as an adaptor protein for IkappaBalpha degradation in UV-induced NF-kappaB activation. NF-kappaB activated by the nuclear IKKbeta adaptor protein suppresses anti-apoptotic gene expression and promotes UV-induced cell death.
Mesh Terms:
Active Transport, Cell Nucleus, Animals, Apoptosis, Casein Kinase II, Cell Line, Cell Nucleus, Fibroblasts, Heterogeneous-Nuclear Ribonucleoprotein U, Humans, I-kappa B Kinase, I-kappa B Proteins, Mice, Mice, Knockout, Mutation, NF-kappa B, Phosphorylation, Protein Processing, Post-Translational, Time Factors, Transcription Factor RelA, Transfection, Ubiquitination, Ultraviolet Rays, beta-Transducin Repeat-Containing Proteins, p38 Mitogen-Activated Protein Kinases
Active Transport, Cell Nucleus, Animals, Apoptosis, Casein Kinase II, Cell Line, Cell Nucleus, Fibroblasts, Heterogeneous-Nuclear Ribonucleoprotein U, Humans, I-kappa B Kinase, I-kappa B Proteins, Mice, Mice, Knockout, Mutation, NF-kappa B, Phosphorylation, Protein Processing, Post-Translational, Time Factors, Transcription Factor RelA, Transfection, Ubiquitination, Ultraviolet Rays, beta-Transducin Repeat-Containing Proteins, p38 Mitogen-Activated Protein Kinases
Mol. Cell
Date: Aug. 27, 2010
PubMed ID: 20797629
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