title: Signal-specific and phosphorylation-dependent RelB degradation: a potential mechanism of NF-kappaB control.
abstract: RelB is an unusual member of the Rel/NF-kappaB family of transcription factors which are involved in oncogenic processes. Due to a relaxed control by the IkappaBs, the cytosolic NF-kappaB inhibitors, RelB is constitutively expressed in the nuclei of lymphoid cells. We show here that RelB is inducibly degraded upon activation of T cells in a fashion similar to the IkappaBs. However, RelB degradation differs from that of IkappaBs since it is not induced by TNFalpha but only by T cell receptor or TPA/ionomycin stimulation. Moreover, RelB degradation occurs in three steps: (i) after stimulation RelB is rapidly phosphorylated at amino acids Thr84 and Ser552 followed by (ii) an N-terminal cut and, finally, (iii) the complete degradation in the proteasomes. Since mutation of the two phosphoacceptor sites to non-acceptor sites abolished RelB phosphorylation in vivo and led to the stabilization of the mutated RelB(DM), site-specific phosphorylation appears to be a necessary prerequisite for RelB degradation. RelB is a crucial regulator of NF-kappaB-dependent gene expression. Thus, the signal-induced degradation of RelB should be an important control mechanism of NF-kappaB activity.
authors.affiliation: Department of Molecular Pathology, Institute of Pathology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Marienfeld
authors.forename: F
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: I
authors.initials: I
authors.lastname: Berberich
authors.forename: A
authors.initials: A
authors.lastname: Denk
authors.forename: E
authors.initials: E
authors.lastname: Serfling
authors.forename: M
authors.initials: M
authors.lastname: Neumann
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D051379:Mice; D009097:Multienzyme Complexes / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D009097:Multienzyme Complexes; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D011948:Receptors, Antigen, T-Cell; C497594:Relb protein, mouse; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051841:Transcription Factor RelB; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex