Inhibition of NF-κB Acetylation and its Transcriptional Activity by Daxx

Park, Jinhwi; Lee, Jae Ho; La, Muhnho; Jang, Moon Jung; Chae, Gil Woo; Kim, Seung Beom; Tak, Heejae; Jung, Yunhwa; Byun, Boohyeong; Ahn, Jeong Keun; Joe, Cheol O.

doi:10.1016/j.jmb.2007.02.047

Cited by 51 publications

(39 citation statements)

References 37 publications

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“…Previous studies have shown that Daxx can inhibit p65 transactivation, correlating with the inhibition of p65 acetylation in HeLa cells (36). However, in our study, we found expression of IL-12p40, also a target of p65, was not affected when Daxx was silenced.…”

Section: Discussioncontrasting

confidence: 67%

Death Domain-associated Protein 6 (Daxx) Selectively Represses IL-6 Transcription through Histone Deacetylase 1 (HDAC1)-mediated Histone Deacetylation in Macrophages

Yao

Zhang

et al. 2014

Journal of Biological Chemistry

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Background:The role and underlying mechanism of Daxx in innate immunity remain to be investigated. Results: Daxx interacts with HDAC1 and binds to the promoter of IL-6. Daxx selectively represses IL-6 transcription through HDAC1-mediated histone deacetylation. Conclusion: Daxx selectively represses IL-6 transcription in TLR-triggered macrophages. Significance: Discovering a new negative regulator of IL-6 and providing insight to epigenetic mechanism of IL-6 production.

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Section: Discussioncontrasting

confidence: 67%

Death Domain-associated Protein 6 (Daxx) Selectively Represses IL-6 Transcription through Histone Deacetylase 1 (HDAC1)-mediated Histone Deacetylation in Macrophages

Yao

Zhang

et al. 2014

Journal of Biological Chemistry

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“…As determined by densitometry on the Western blots, there was a 3.1-fold elevation in nuclear RelA levels in nonstimulated macrophages lacking Ing4. EMSA were performed with these nuclear extracts using a canonical RelA-NF-κB-binding DNAsequence motif (23). The results revealed increased RelA binding in untreated Ing4 −/− macrophage nuclear extracts relative to untreated WT extracts, and increased RelA DNA binding at 30 or 60 min after LPS treatment relative to WT cells (Fig.…”

Section: Ing4-null Macrophages Display Elevated Expression Of Nf-κb-mentioning

confidence: 90%

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Coles¹,

Gannon²,

Cerny³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Ing4 is a member of the inhibitor of growth (ING) family of chromatin-modifying proteins. Biochemical experiments indicate that Ing4 is a subunit of the HB01-JADE-hEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation in eukaryotes, and transfection studies suggest that Ing4 may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression. However, in vivo evidence for a physiological role for Ing4 in cell-growth regulation is lacking. We have generated Ing4-deficient mice to explore the role of Ing4 in development, tumorigenesis, and in NF-κB signaling. Ing4-null mice develop normally and are viable. Although mice deficient for Ing4 fail to form spontaneous tumors, they are hypersensitive to LPS treatment and display elevated cytokine responses. Macrophages isolated from Ing4-null mice have increased levels of nuclear p65/RelA protein, resulting in increased RelA binding to NF-κB target promoters and up-regulation of cytokine gene expression. However, increased promoter occupancy by RelA in LPS-stimulated, Ing4-null cells does not always correlate with increased NF-κB target-gene expression, as RelA activation of a subset of cytokine promoters also requires Ing4 for proper histone H4 acetylation. Furthermore, activation of the IκBα promoter by RelA is also Ing4-dependent, and LPS-stimulated, Ing4-null cells have reduced levels of IκBα promoter H4 acetylation and IκB gene expression. Thus, Ing4 negatively regulates the cytokine-mediated inflammatory response in mice by facilitating NF-κB activation of IκB promoters, thereby suppressing nuclear RelA levels and the activation of select NF-κB target cytokines.

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“…Thus, it has been implicated to modulate principle aspects of apoptosis, as well as repression of basal transcription. Thus far, many factors known to play critical roles in controlling programmed cell death and gene expression have been shown to associate with Daxx, including the serine/threonine-specific protein kinases HIPK1, HIPK3, and ZIPK (40,48,84,98); the specific transcription factors p14 ARF , Ets-1, Pax3, Pax5, NF-B, and Smad4 (8,18,42,60,78); and the chromatin-associated factors HDAC2, H2A, H2B, H3, H4, Dek, HIPK2, and ATRX (41,102,114). Initially, Daxx was identified as a protein that binds to the Fas death domain receptor (CD95/Apo-1).…”

mentioning

confidence: 99%

Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells

Schreiner

Wimmer

Groitl

et al. 2011

J Virol

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Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributes in vitro to complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription.Previous reports demonstrated that DNA tumor virus genomes preferentially target subnuclear host cell structures called promyelocytic leukemia nuclear bodies (PML-NBs) immediately after infection. These domains represent sites of active viral gene transcription and most are also presumably sites of oncogenic processes (6,44,45,66,113). As we and others reported previously, the transcriptional repressor Daxx (death domain-associated protein) is a principal component of the PML-NBs and a negative regulator of adenovirus type 5 (Ad5) replication in productive infection (94,106).Daxx is a ubiquitously expressed vertebrate polypeptide that mediates a variety of cellular functions (115). Thus, it has been implicated to modulate principle aspects of apoptosis, as well as repression of basal transcription. Thus far, many factors known to play critical roles in controlling programmed cell death and gene expression have been shown to associate with Daxx, including the serine/threonine-specific protein kinases HIPK1, HIPK3, and ZIPK (40,48,84,98); the specific transcription factors p14 ARF , Ets-1, Pax3, Pax5, NF-B, and Smad4 (8,18,42,60,78); and the chromatin-associated factors HDAC2, H2A, H2B, H3, H4, Dek, HIPK2, and ATRX (41,102,114). Ini...

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Inhibition of NF-κB Acetylation and its Transcriptional Activity by Daxx

Cited by 51 publications

References 37 publications

Death Domain-associated Protein 6 (Daxx) Selectively Represses IL-6 Transcription through Histone Deacetylase 1 (HDAC1)-mediated Histone Deacetylation in Macrophages

Death Domain-associated Protein 6 (Daxx) Selectively Represses IL-6 Transcription through Histone Deacetylase 1 (HDAC1)-mediated Histone Deacetylation in Macrophages

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells

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