Control of NF-κB Activity by the IκBβ Inhibitor

• Published in: Immunobiology (1979) 1997-12, Vol.198 (1), p.14-23
• Main Authors: Weil, Robert, Whiteside, Simon T., IsraÈl, Alain
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Cell Line; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - metabolism; Humans; I-kappa B Proteins; Mice; NF-kappa B - antagonists & inhibitors; NF-KappaB Inhibitor alpha; Phosphorylation; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/S0171-2985(97)80023-X

The transcription factor NF-κB is maintained in an inactive cytoplasmic state by IκB inhibitors.In mammalian cells, IκBα and IκBβ proteins have been purified and shown to be the inhibitors of NF-κB through their association with the p65 or c-Rel subunits. In addition, we have isolated a third NF-κB inhibitor, IκBε (1). Upon treatment with a large variety of inducers, IκBα, IκBβ are proteolytically degraded, resulting in NF-κB translocation into the nucleus. Here we show that in E29.1 T cell hybridoma IKBα and IκBβ are equally associated with p65 and that IκBβ is degraded in response to TNFα in contrast to what has been originally published. Our data also suggest that, unlike IκBα, IκBβ is constitutively phosphorylated and resynthesized as a hypophosphorylated form. The absence of slow migrating forms of IκBβ following stimulation suggests that the phosphorylation does not necessarily constitute the signal-induced event which targets the molecule for proteolysis.