Inhibition of Transcription by B Cell Leukemia 3 (Bcl-3) Protein Requires Interaction with Nuclear Factor κB (NF-κB) p50

Collins, Patricia E.; Kiely, Patrick A.; Carmody, Ruaidhrı́ J.

doi:10.1074/jbc.m114.551986

Cited by 49 publications

(53 citation statements)

References 27 publications

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“…Interaction with p50 is necessary and sufficient for this antiinflammatory function of BCL-3 (14). To further investigate the role of this complex in the regulation of NF-B-mediated gene transcription we employed a BCL-3 peptomimetic strategy.…”

Section: Discussionmentioning

confidence: 99%

“…Neither of these two regions of BCL-3 are represented in the available BCL-3 crystal structure, however, the in silico models of BCL-3:p50 homodimers would suggest that they may interact with the C-terminal region of p50 (15,20). In addition, we have recently demonstrated the C-terminal region of p50 and in particular amino acids 359 -361 and 363, to be required for interaction with BCL-3 (14). This, combined with the peptide data presented here suggests that the N terminus and ANK1 of BCL-3 may mediate the interaction with the C-terminal region of p50 to promote the formation of a BCL-3⅐p50 homodimer complex.…”

Section: Comparison Of Peptide Array and In Silico Analysis Of Bcl-3/p50mentioning

confidence: 99%

“…These structures do not represent the entire BCL-3 and p50 protein sequences and so these models lack information on the C-and N-terminal regions of both proteins. We recently employed a peptide array based technique to identify amino acids of p50 that mediate interaction with BCL-3 (14). Here, we took a similar approach to identify amino acids of BCL-3 that mediate interaction with p50 homodimers.…”

Section: Analysis Of Bcl-3/p50mentioning

confidence: 99%

“…We recently employed peptide array techniques to identify critical amino acids of p50, which mediate the interaction with BCL-3 (14). In this study we employ similar techniques to identify residues of BCL-3, which mediate interaction with p50.…”

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confidence: 99%

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Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide

Collins

Grassia

Colleran

et al. 2015

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Peptide Array and In Silico Analysis Of Bcl-3/p50mentioning

confidence: 99%

Section: Analysis Of Bcl-3/p50mentioning

confidence: 99%

mentioning

confidence: 99%

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Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide

Collins

Grassia

Colleran

et al. 2015

Journal of Biological Chemistry

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“…Among the downregulated genes, the bcl-3 gene was most strongly downregulated both in SeAx and HH cells ( Figure 2F). Bcl-3 exerts its influence on transcription via interaction with p50 40,41 and is needed for CTCL survival. 42 In other T-cell lymphoma types, Bcl-3 activity is increased by translocations and chromosomal gains, resulting in increased NF-kB activity.…”

Section: Dmf Induces Cell Death In Patient-derived Ctcl and Ctcl Cellmentioning

confidence: 99%

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Nicolay

Müller‐Decker

Schroeder

et al. 2016

Blood

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Key Points• DMF induces specific cell death in CTCL cells and inhibits CTCL tumor growth and metastasis in vivo via inhibition of NF-kB.• DMF therefore represents a promising, nontoxic novel therapeutic approach to treating CTCL.Despite intensive efforts in recent years, a curative therapy for cutaneous T-cell lymphoma (CTCL) has not yet been developed. Therefore, the establishment of new therapeutic approaches with higher efficacy rates and milder side effects is strongly desired. A characteristic feature of the malignant T-cell population in CTCL is resistance toward cell death resulting from constitutive NF-kB activation. Therefore, NF-kBdependent cell death resistance represents an interesting therapeutic target in CTCL because an NF-kB-directed therapy would leave bystander T cells widely unaffected. We investigated the effects of dimethyl fumarate (DMF) on CTCL cells in vitro and in vivo. DMF induced cell death in primary patient-derived CD4 1 cells and CTCL cell lines, but hardly in T cells from healthy donors. DMF-induced cell death was linked specifically to NF-kB inhibition. To study the impact of DMF in vivo, we developed 2 CTCL xenograft mouse models with different cutaneous localizations of the T-cell infiltrate. DMF treatment delayed the growth of CTCL tumors and prevented formation of distant metastases. In addition, DMF induced increased cell death in primary CTCL tumors and in liver metastases. In summary, DMF treatment represents a remarkable therapeutic option in CTCL because it restores CTCL apoptosis in vitro and in preclinical models in vivo and prevents spreading of the disease to distant sites. DMF treatment is of particular promise in CTCL because DMF is already in successful clinical use in the treatment of psoriasis and multiple sclerosis allowing fast translation into clinical studies in CTCL. (Blood. 2016;128(6):805-815)

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Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism

et al. 2018

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The induced expression of nitric oxide synthase (iNOS) controls the intracellular growth of Leishmania in infected macrophages. Histones deacetylases (HDACs) negatively regulate gene expression through the formation of complexes containing transcription factors such as NF-κB p50/50. Herein, we demonstrated the occupancy of p50/p50_HDAC1 to iNOS promoter associated with reduced levels of H3K9Ac. Remarkably, we found increased levels of HDAC1 in L. amazonensis-infected macrophages. HDAC1 upregulation was not found in L. major-infected macrophages. The parasite intracellular load was reduced in HDAC1 knocked-down macrophages, which presented increased nitric oxide levels. HDAC1 silencing led to the occupancy of CBP/p300 to iNOS promoter and the rise of H3K9Ac modification. Importantly, the immunostaining of skin samples from hiporeactive cutaneous leishmaniasis patients infected with L. amazonensis, revealed high levels of HDAC1. In brief, L. amazonensis induces HDAC1 in infected macrophages, which contribute to parasite survival and is associated to hiporeactive stage found in L. amazonensis infected patients.

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Inhibition of Transcription by B Cell Leukemia 3 (Bcl-3) Protein Requires Interaction with Nuclear Factor κB (NF-κB) p50

Cited by 49 publications

References 27 publications

Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide

Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide

Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB

Leishmania amazonensis downregulates macrophage iNOS expression via Histone Deacetylase 1 (HDAC1): a novel parasite evasion mechanism

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