Overexpression of RelB in transgenic mice does not affect I kappa B alpha levels: differential regulation of RelA and RelB by the inhibitor protein.
In mouse lymphoid tissues, RelB heterodimers represent the constitutive kappa B-binding activity, whereas RelA and c-Rel complexes most likely are involved in inducible kappa B-binding and gene activation. Our laboratory has previously shown that the potential excess of NF-kappa B activity in transgenic mice overexpressing RelA is counteracted by a dramatic increase in I kappa B alpha, mainly due to its increased stability through association with RelA. As an attempt to elucidate the in vivo mechanisms that lead to the constitutive DNA-binding activity of RelB heterodimers, we have generated mouse lines overexpressing a relB transgene in a position-independent and copy number-dependent manner. Expression of RelB in these transgenic animals is very high in immature thymocytes and restricted to T cell areas in secondary lymphoid tissues. In contrast to the results obtained with RelA-transgenic thymocytes, we demonstrate here that overexpression of RelB results in a dramatic increase in overall kappa B-binding activity. Interestingly, I kappa B alpha protein levels are not altered in the RelB-transgenic animals, indicating that within the same cell type RelA and RelB complexes are differentially regulated by I kappa B alpha.
Weih
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Department of Molecular Oncology, Bristol-Myers Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Lira
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Bravo
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D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D020672:I-kappa B Proteins; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D051841:Transcription Factor RelB