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- W2169668745 abstract "Constitutive NF-kappaB activity has emerged as an important cell survival component of physiological and pathological processes, including B-cell development. In B cells, constitutive NF-kappaB activity includes p50/c-Rel and p52/RelB heterodimers, both of which are critical for proper B-cell development. We previously reported that WEHI-231 B cells maintain constitutive p50/c-Rel activity via selective degradation of IkappaBalpha that is mediated by a proteasome inhibitor-resistant, now termed PIR, pathway. Here, we examined the mechanisms of PIR degradation by comparing it to the canonical pathway that involves IkappaB kinase-dependent phosphorylation and beta-TrCP-dependent ubiquitylation of the N-terminal signal response domain of IkappaBalpha. We found a distinct consensus sequence within this domain of IkappaBalpha for PIR degradation. Chimeric analyses of IkappaBalpha and IkappaBbeta further revealed that the ankyrin repeats of IkappaBalpha, but not IkappaBbeta, contained information necessary for PIR degradation, thereby explaining IkappaBalpha selectivity for the PIR pathway. Moreover, we found that PIR degradation of IkappaBalpha and constitutive p50/c-Rel activity in primary murine B cells were maintained in a manner different from B-cell-activating-factor-dependent p52/RelB regulation. Thus, our findings suggest that nonconventional PIR degradation of IkappaBalpha may play a physiological role in the development of B cells in vivo." @default.
- W2169668745 created "2016-06-24" @default.
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- W2169668745 creator A5049365231 @default.
- W2169668745 creator A5057447059 @default.
- W2169668745 creator A5082665802 @default.
- W2169668745 date "2004-06-01" @default.
- W2169668745 modified "2023-09-27" @default.
- W2169668745 title "Regulation of Constitutive p50/c-Rel Activity via Proteasome Inhibitor-Resistant IκBα Degradation in B Cells" @default.
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- W2169668745 doi "https://doi.org/10.1128/mcb.24.11.4895-4908.2004" @default.
- W2169668745 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/416427" @default.
- W2169668745 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15143182" @default.
- W2169668745 hasPublicationYear "2004" @default.
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