title: Tumor suppressor p53 functions as a negative regulator in IgE-mediated mast cell activation.
abstract: Mast cells are known to play a pivotal role in allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis by releasing granules containing histamine, LTC4, and other preformed chemical mediators. Previous reports have demonstrated that IKK2 (also called IKKβ), a central intracellular component of NF-κB activation pathways, plays a critical role in IgE-mediated degranulation of mast cells and anaphylaxis in mice. In this study, we show that protein levels of tumor suppressor p53 are up-regulated upon IgE-mediated activation in mast cells and lack of p53 results in enhanced responses in both early and late phase anaphylaxis. p53 inhibits not only the catalytic activity of IKK2 presumably through the modulation of glycosylation but also p65 (RelA)-mediated transactivation. Our findings are the first to demonstrate that p53 functions as a negative regulator in mast cells.
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, United States of America. suzuki_k@faculty.chiba-u.jp
authors.forename: Kotaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Samantha H
authors.initials: SH
authors.lastname: Murphy
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Masaya
authors.initials: M
authors.lastname: Yokota
authors.forename: Daiki
authors.initials: D
authors.lastname: Nakagomi
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005434:Flow Cytometry; D006031:Glycosylation; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D007073:Immunoglobulin E; D051550:I-kappa B Kinase