RelB cellular regulation and transcriptional activity are regulated by p100
- PMID: 11687592
- DOI: 10.1074/jbc.M109619200
RelB cellular regulation and transcriptional activity are regulated by p100
Abstract
RelB mediates the constitutive nuclear pool of NF-kappaB transcriptional activity in myeloid and lymphoid cells, which is believed to be secondary to its weak interaction with the classical NF-kappaB inhibitor proteins, the IkappaBs. In other cell types, RelB is located in the cytosol, thus suggesting that RelB is also regulated by an inhibitory protein(s). In this study, it is demonstrated that RelB is associated in the cytosol with p100 but not with IkappaBalpha, IkappaBbeta, IkappaBepsilon, nor p105. Its cytosolic control is not affected by stimuli that lead to RelA nuclear translocation, and RelB nuclear localization is prevented by p100, but not by p105 or IkappaBalpha. Structure function analysis p100-RelB interactions indicates that p100 amino acids 623-900 are required for effective interaction and repression of nuclear translocation and RelB driven NF-kappaB-dependent transcription. Moreover, this carboxyl-portion of p100 contains a nuclear export signal(s), which is required for effective retrieval of RelB from the nucleus. Finally, overexpression of NF-kappaB-inducing kinase, a kinase that has recently been shown to induce p100 processing, possibly through IKKalpha activation, causes nuclear translocation of RelB protein. Thus, these studies indicate that p100 is a bone fide inhibitor of RelB and that this transcription factor may be regulated by NF-kappaB-inducing kinase and/or IKKalpha.
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