Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha determine pools of constitutive and inducible NF-kappa B activity.
The Rel-NF-kappa B family of transcription factors plays a crucial role in the regulation of genes involved in inflammatory and immune responses. We demonstrate that in vivo, in contrast to the other members of the family, RelB associates efficiently only with NF-kappa B1 (p105-p50) and NF-kappa B2 (p100-p52), but not with cRel or p65. The RelB-p52 heterodimers display a much lower affinity for I kappa B alpha than RelB-p50 heterodimers or p65 complexes. However, similarly to the other Rel-NF-kappa B complexes, RelB-p52 can upregulate the synthesis of I kappa B alpha leading to the cytoplasmic trapping of dimers which have a higher affinity for the inhibitor. We suggest that a hierarchy of interactions between I kappa B alpha and the different Rel-NF-kappa B complexes governs their cellular distribution. This results in the presence of two distinct pools of NF-kappa B activity which differ in their composition: one a constitutive nuclear and the other an inducible cytoplasmic activity.
Dobrzanski
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Department of Molecular Biology, Bristol-Myers-Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Ryseck
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Bravo
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D001402:B-Lymphocytes / Q000378:metabolism; D001704:Biopolymers; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D001704:Biopolymers; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB