RelB Cellular Regulation and Transcriptional Activity Are Regulated by p100
RelB mediates the constitutive nuclear pool of NF-κB transcriptional activity in myeloid and lymphoid cells, which is believed to be secondary to its weak interaction with the classical NF-κB inhibitor proteins, the IκBs. In other cell types, RelB is located in the cytosol, thus suggesting that R...
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Published in | The Journal of biological chemistry Vol. 277; no. 2; pp. 1405 - 1418 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
11.01.2002
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Subjects | |
Online Access | Get full text |
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Summary: | RelB mediates the constitutive nuclear pool of NF-κB transcriptional activity in myeloid and lymphoid cells, which is believed
to be secondary to its weak interaction with the classical NF-κB inhibitor proteins, the IκBs. 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 IκBα, IκBβ, IκBε, 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
IκBα. Structure function analysis p100-RelB interactions indicates that p100 amino acids 623â900 are required for effective
interaction and repression of nuclear translocation and RelB driven NF-κB-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-κB-inducing kinase, a kinase that has recently been shown to induce p100 processing, possibly through
IKKα 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-κB-inducing kinase and/or IKKα. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M109619200 |