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- _5 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _4 value "Nuclear factor-kappaB (NF-kappaB) is a transcription factor critical for key cellular processes, including immune response, apoptosis, and cell cycle progression. A yeast two-hybrid screening, using the Rel homology domain (RHD) of the p65 subunit (RelA) of NF-kappaB as bait, led to the isolation of PIAS3, previously identified as a specific inhibitor of STAT3. We show that PIAS3 can directly associate with p65 using an in vitro pull-down and in vivo coimmunoprecipitation assays. When overexpressed, PIAS3 inhibits NF-kappaB-dependent transcription induced by treatment with tumor necrosis factor alpha (TNF-alpha) or interleukin-1beta or by overexpression of TNF family receptors such as RANK, TNFR1, and CD30 or signal transducers of TNF receptor-associated factors (TRAFs), including TRAF2, TRAF5, and TRAF6. Downregulation of PIAS3 by RNA interference reverses its effect on TNF-alpha-mediated NF-kappaB activation. We found that an N-terminal region of PIAS3 is necessary for both the interaction with p65 and the transcriptional suppression activity. In addition, we found that an LXXLL coregulator signature motif located within the N-terminal region of PIAS3 is the minimal requirement for the interaction with p65. Furthermore, we demonstrate that PIAS3 interferes with p65 binding to the CBP coactivator, thereby resulting in a decreased NF-kappaB-dependent transcription. Taken together, these data suggest that PIAS3 may function in vivo as a modulator in suppressing the transcriptional activity of p65." provenance.
- _4 wasQuotedFrom 15140884 provenance.
- assertion hadPrimarySource 15140884 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom _4 provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- large_corpus.bel authoredBy _5 provenance.
- large_corpus.bel version "20131211" provenance.