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NF-kappa B p100 is one of the high-molecular-weight proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells.

ABSTRACT: The Rel/NF-kappa B family of proteins includes several interacting cellular transcription factors and the v-Rel oncoprotein of the avian Rev-T retrovirus. We report the isolation of a chicken cDNA for the NF-kappa B p52 precursor protein p100. Full-length p100 only weakly binds DNA in vitro; removal of the ankyrin-like repeats generates C-terminally truncated p100 proteins (like p52) that have an increased ability to bind an oligonucleotide containing a kappa B site. In addition, we show that chicken p100 is identical to a protein previously designated p115, which is found in a complex with v-Rel in transformed chicken spleen cells. Furthermore, p100 and v-Rel can form a complex when synthesized in vitro. Using cDNAs for chicken NF-kappa B p105, NF-kappa B p100, c-Rel, and v-Rel, we show that one of the complexes in v-Rel-transformed spleen cells can be reconstituted in vitro.

SUBMITTER: Sif S

PROVIDER: S-EPMC238228 | biostudies-other | 1993 Dec

REPOSITORIES: biostudies-other

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NF-kappa B p100 is one of the high-molecular-weight proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells.

Sif S S Gilmore T D TD

Journal of virology 19931201 12

The Rel/NF-kappa B family of proteins includes several interacting cellular transcription factors and the v-Rel oncoprotein of the avian Rev-T retrovirus. We report the isolation of a chicken cDNA for the NF-kappa B p52 precursor protein p100. Full-length p100 only weakly binds DNA in vitro; removal of the ankyrin-like repeats generates C-terminally truncated p100 proteins (like p52) that have an increased ability to bind an oligonucleotide containing a kappa B site. In addition, we show that ch ...[more]

PMID: 8230480

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Project description:Proper regulation of nuclear factor κB (NF-κB) transcriptional activity is required for normal lymphocyte function, and deregulated NF-κB signaling can facilitate lymphomagenesis. We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma induces proteolytic cleavage of NF-κB–inducing kinase (NIK) at arginine 325. NIK cleavage requires the concerted actions of both fusion partners and generates a C-terminal NIK fragment that retains kinase activity and is resistant to proteasomal degradation. The resulting deregulated NIK activity is associated with constitutive noncanonical NF-κB signaling, enhanced B cell adhesion, and apoptosis resistance. Our study reveals the gain-of-function proteolytic activity of a fusion oncoprotein and highlights the importance of the noncanonical NF-κB pathway in B lymphoproliferative disease. This study compares nine t(11;18)-positive MALT lymphomas (8 from the stomach and 1 from lung) and eight translocation negative MALT lymphomas (all from the stomach) using gene set enrichment analysis (GSEA). All cases were subjected to Affymetrix U133A and U133B microarray analysis. The cases used in this study are the same cases used for the study by Hamoudi et al. (2010) entitled "Differential expression of NF-kB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism" with GEO reference number: GSE18736 and PubMed ID: http://www.ncbi.nlm.nih.gov/pubmed/20520640 All cases were subjected to non-specific filtering to eliminate non-variant probes, then the U133A and U133B probes were collapsed and the collapsed set was subjected to GSEA using the NF-kB target gene set as described in Hamoudi et al. (2010) study mentioned above. The 34 samples in this study are identical to the ones done in the previous series except that the gene set enrichment was done on just those 34 samples and not the complete set.

Project description:Tumor necrosis factor (TNF) is a pleiotropic cytokine whose primary physiological function involves coordinating inflammatory and adaptive immune responses. However, uncontrolled TNF signaling causes aberrant inflammation and has been implicated in several human ailments. Therefore, an understanding of the molecular mechanisms underlying dynamical and gene controls of TNF signaling bear significance for human health. As such, TNF engages the canonical nuclear factor kappa B (NF-κB) pathway to activate RelA:p50 heterodimers, which induce expression of specific immune response genes. Brief and chronic TNF stimulation produces transient and long-lasting NF-κB activities, respectively. Negative feedback regulators of the canonical pathway, including IκBα, are thought to ensure transient RelA:p50 responses to short-lived TNF signals. The non-canonical NF-κB pathway mediates RelB activity during immune differentiation involving p100. We uncovered an unexpected role of p100 in TNF signaling. Brief TNF stimulation of p100-deficient cells triggered an additional late NF-κB activity consisting of RelB:p50 heterodimers, which modified the TNF-induced gene-expression program. In p100-deficient cells subjected to brief TNF stimulation, RelB:p50 not only sustained the expression of a subset of RelA-target immune response genes but also activated additional genes that were not normally induced by TNF in WT mouse embryonic fibroblasts (MEFs) and were related to immune differentiation and metabolic processes. Despite this RelB-mediated distinct gene control, however, RelA and RelB bound to mostly overlapping chromatin sites in p100-deficient cells. Repeated TNF pulses strengthened this RelB:p50 activity, which was supported by NF-κB-driven RelB synthesis. Finally, brief TNF stimulation elicited late-acting expressions of NF-κB target pro-survival genes in p100-deficient myeloma cells. In sum, our study suggests that the immune-differentiation regulator p100 enforces specificity of TNF signaling and that varied p100 levels may provide for modifying TNF responses in diverse physiological and pathological settings.

Dataset Information

NF-kappa B p100 is one of the high-molecular-weight proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells.

Publications

NF-kappa B p100 is one of the high-molecular-weight proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells.

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