title: Transcription of the RelB gene is regulated by NF-kappaB.
abstract: RelA and RelB are two members of the NF-kappaB family that differ structurally and functionally. While RelA is regulated through its cytosolic localization by inhibitor proteins or IkappaB and not through transcriptional mechanisms, the regulation of RelB is poorly understood. In this study we demonstrate that stimuli (TNF or LPS) lead within minutes to the nuclear translocation of RelA, but require hours to result in the nuclear translocation of RelB. The delayed nuclear translocation of RelB correlates with increases in its protein synthesis which are secondary to increases in RelB gene transcription. RelA is alone sufficient to induce RelB gene transcription and to mediate the stimuli-driven increase in RelB transcription. Cloning and characterization of the RelB 5' untranslated gene region indicates that RelB transcription is dependent on a TATA-less promoter containing two NF-kappaB binding sites. One of the NF-kappaB sites is primarily involved in the binding of p50 while the other one in the binding and transactivation by RelA and also RelB. Lastly, it is observed that p21, a protein involved in cell cycle control and oncogenesis known to be regulated by NF-kappaB, is upregulated at the transcriptional level by RelB. Thus, RelB is regulated at least at the level of transcription in a RelA and RelB dependent manner and may exert an important role in p21 regulation.
authors.affiliation: Department of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Bren
authors.forename: N J
authors.initials: NJ
authors.lastname: Solan
authors.forename: H
authors.initials: H
authors.lastname: Miyoshi
authors.forename: K N
authors.initials: KN
authors.lastname: Pennington
authors.forename: L J
authors.initials: LJ
authors.lastname: Pobst
authors.forename: C V
authors.initials: CV
authors.lastname: Paya
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
chemical_list: D020121:5' Untranslated Regions; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051841:Transcription Factor RelB