The Interaction of Pax5 (BSAP) with Daxx Can Result in Transcriptional Activation in B Cells

Emelyanov, Alexander; Kovac, Cecilia; Sepúlveda, Manuel A.; Birshtein, Barbara K.

doi:10.1074/jbc.m111763200

Cited by 102 publications

(104 citation statements)

References 58 publications

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“…Dependent on the cellular and the molecular context, Daxx acts as a transcriptional corepressor 8,[105][106][107] or coactivator. 108 Several laboratories demonstrated that Daxx localises to the nucleus where it is found in association with chromatin, centromeres and PML-NBs. 8,[105][106][107]109 The subcellular localisation of Daxx can be regulated by its interaction with the kinase ASK1, which recruits Daxx independent of its kinase activity to the cytoplasm.…”

Section: Daxxmentioning

confidence: 99%

“…116 Future studies are needed to clarify the discrepancies in the role of Daxx in apoptosis, in particular considering a possible cell typespecific function, which might in part be explained by its molecular context-dependent gene repressive or stimulatory function. 108 Since Daxx also interacts with p53, 117 it would be interesting to study whether the apoptosis in Daxx-deficient mice depends on p53, and whether Daxx might serve as a corepressor for unrestrained p53 activation during development. In this respect, it is interesting to note that Daxx can repress the transactivating potential of the transcription factor Ets-1, 106 which in turn appears to be essential for stressinduced p53 target gene expression as revealed by experiments with Ets-1-deficient embryonic stem cells.…”

Section: Daxxmentioning

confidence: 99%

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Body language: the function of PML nuclear bodies in apoptosis regulation

2003

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Promyelocytic leukaemia (PML) nuclear bodies (NBs) are macromolecular nuclear domains present in virtually every mammalian cell. PML nuclear bodies (PML-NBs) were functionally linked to various fundamental cellular processes, including transcriptional control, tumour suppression and apoptosis regulation. Supporting the important function of PML and its associated NBs in apoptosis regulation, several apoptotic regulators localise to PML-NBs, and cells from PMLdeficient mice show severe apoptotic defects, including induction of genotoxic stress and death receptor CD95 (Fas/ APO-1) activation. Based on the current literature, we hypothesise that PML-NBs regulate apoptosis through different molecular mechanisms, on the one hand by acting as macromolecular scaffolds for recruitment and post-translational modification of the apoptotic key regulator p53, and on the other by regulating the subcellular bioavailability and quality of some apoptotic signal transducers.

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Section: Daxxmentioning

confidence: 99%

Section: Daxxmentioning

confidence: 99%

Body language: the function of PML nuclear bodies in apoptosis regulation

2003

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“…Recent studies also demonstrated that Daxx might function as a transcriptional co-regulator for several transcription factors such as Pax3, ETS1 and GR through direct protein-protein interactions (4,6,10). Daxx recruits nuclear factors possessing either histone acetyltransferase or HDAC activity to modulate transcriptional activity (5,9,35). In fact, Daxx is shown to bind to HDAC2 (9,35).…”

Section: Discussionmentioning

confidence: 99%

“…While the interaction between Daxx and Fas indicated the importance of Daxx in cytoplasm, nuclear localization of Daxx was observed in various cell lines and the interactions of Daxx with several nuclear proteins such as the centromeric protein CENP-C, DNA methyltransferase 1 (DNMT1), Pax-3, Pax-5, ETS1, Ubc9, SUMO-1 and PML were reported (2)(3)(4)(5)(6)(7)(8)(9). These studies suggest that Daxx may play a role in the nucleus and it has been reported that it functions as a transcriptional co-regulator by interaction with various transcription factors.…”

Section: Introductionmentioning

confidence: 99%

“…Daxx is also shown to act as a transcriptional co-activator or co-repressor of Pax5 in different cell types (5). Although the exact mechanism accounting for these observations is still unclear, the recruitment of nuclear factors possessing either histone acetyltransferase or histone deacetylase (HDAC) activity by Daxx to modulate Pax5 transcriptional activity was proposed (5). In addition, the transcriptional repression effect of Daxx could be modulated by subnuclear or subcellular compartmentalization through protein-protein interactions (11,12,13).…”

Section: Introductionmentioning

confidence: 99%

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Physical and functional interactions between Daxx and TSG101

Muromoto

Sugiyama

Yamamoto

et al. 2004

Biochemical and Biophysical Research Communications

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Functional involvement of Daxx in gp130‐mediated cell growth and survival in BaF3 cells

et al. 2010

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Death domain-associated protein (Daxx) is a multifunctional protein that modulates both cell death and transcription. Several recent studies have indicated that Daxx is a mediator of lymphocyte death and/or growth suppression, although the detailed mechanism is unclear. Previously, we reported that Daxx suppresses IL-6 family cytokine-induced gene expression by interacting with STAT3. STAT3 is important for the growth and survival of lymphocytes; therefore, we here examined the role of Daxx in the gp130/STAT3-dependent cell growth/survival signals. We found that Daxx suppresses the gp130/STAT3-dependent cell growth and that Daxx endogenously interacts with STAT3 and inhibits the DNA-binding activity of STAT3. Moreover, small-interfering RNA-mediated knockdown of Daxx enhanced the expression of STAT3-target genes and accelerated the STAT3-mediated cell cycle progression. In addition, knockdown of Daxx-attenuated lactate dehydrogenase leakage from cells, indicating that Daxx positively regulates cell death during gp130/STAT3-mediated cell proliferation. Notably, Daxx specifically suppressed the levels of Bcl2 mRNA and protein, even in cytokine-unstimulated cells, indicating that Daxx regulates Bcl2 expression independently of activated STAT3. These results suggest that Daxx suppresses gp130-mediated cell growth and survival by two independent mechanisms: inhibition of STAT3-induced transcription and down-regulation of Bcl2 expression.Key words: Cell death . Daxx . gp130 . IL-6 . STAT3 IntroductionDeath domain-associated protein (Daxx) is a multifunctional protein that modulates both cell death and transcription [1]. Daxx is present in most cell types and is mainly located in the nucleus. Because previous studies have demonstrated that Daxx can bear both proand anti-cell-death activities depending on the stimulus and the cell type [1,2], the precise role of Daxx, in particular its ability to promote or hinder cell death, remains controversial. Nevertheless, in lymphocytes, the following observations indicate that Daxx has procell death and/or growth-suppressing functions. First, Daxx is induced by type I interferon in pro-B cells and is required for interferon-induced apoptosis [3]. Second, in Con A-stimulated splenocytes, Daxx up-regulation and interaction with PML correlate with the induction of B-cell apoptosis [4]. Third, CD40-induced proliferation is profoundly reduced in transgenic B cells over-expressing Daxx [5]. Fourth, analysis of T-cell-specific transgenic mice expressing a dominant negative form of Daxx (Daxx-DN) [18][19][20], and the chromatin-modifying protein a-thalassemia syndrome protein [21,22], it seems possible that Daxx regulates cellular processes by regulating transcription of specific genes under different conditions. We have previously shown that Daxx suppresses STAT3-mediated transcriptional activity and has a role in regulating IL-6 family cytokine signaling and gene induction in several cancer cell lines [16].The IL-6 family of cytokines utilizes the membrane glycoprotein gp130 as a cri...

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The Interaction of Pax5 (BSAP) with Daxx Can Result in Transcriptional Activation in B Cells

Cited by 102 publications

References 58 publications

Body language: the function of PML nuclear bodies in apoptosis regulation

Body language: the function of PML nuclear bodies in apoptosis regulation

Physical and functional interactions between Daxx and TSG101

Functional involvement of Daxx in gp130‐mediated cell growth and survival in BaF3 cells

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