Disease relevance of Daxx

• N protein contains three cysteine residues conserved in all known hantaviruses, as well as structural domains responsible for the RNA binding and presumable interaction with the apoptosis enhancer Daxx [1].

High impact information on Daxx

• Other proteins, notably Daxx, also bind Fas and presumably mediate a FADD-independent apoptotic pathway [2].
• These findings implicate the gene repressor function of Daxx in interferon-induced apoptosis of lymphoid progenitors [3].
• Gene expression profile analysis of interferon-beta-treated progenitor B cells revealed enhanced Daxx expression, with concomitant Daxx protein increase and nuclear body translocation [3].
• An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons [3].
• On DNA damage, Daxx dissociates from Mdm2, which correlates with Mdm2 self-degradation [4].

Biological context of Daxx

• CONCLUSIONS: Limitin suppresses B-cell growth through activation of Tyk2, resulting in the up-regulation and nuclear translocation of Daxx [5].
• Daxx has been shown to play an essential role in type I IFN-mediated suppression of B cell development and apoptosis [6].
• Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation [6].
• Notably, a Daxx-small ubiquitin-related modifier fusion protein exhibited increased nuclear localization and ability to suppress cell growth in Ba/F3 cells [6].
• Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX [7].

Anatomical context of Daxx

• Limitin also induces the expression and nuclear translocation of Daxx, which is essential for IFN-alpha-induced inhibition of B-lymphocyte development [5].
• Murine pro-B cell line Ba/F3 expressing Daxx KA revealed a resistance to the IFN-induced growth suppression [6].
• We have generated transgenic mice expressing a dominant-negative form of Daxx (Daxx-DN) in the T-cell lineage [8].
• We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-kappaB, including cIAP2, in human tumor cell lines [9].

Associations of Daxx with chemical compounds

• It is noteworthy that treatment with an exportin inhibitor, leptomycin B, resulted in nuclear localization of Daxx KA and recovery of the IFN-induced growth suppression in Ba/F3 cells [6].

Physical interactions of Daxx

• Daxx strongly binds with Skip both in vitro and in mammalian cells [10].

Co-localisations of Daxx

• Daxx partially co-localizes with Skip in vivo and changes the cellular distribution of Skip [10].

Regulatory relationships of Daxx

• Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3 [11].

Other interactions of Daxx

• The absence of Tyk2 abrogates this induction of Daxx expression and nuclear translocation [5].
• Moreover, FasL up-regulation is reduced in the presence of transgenic dominant-negative Daxx [12].
• In mutant SOD1(G93A) and SOD1(G85R), but not in control motoneurons, this up-regulation results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis [12].
• Here, we show that the transcription repressor Daxx and the SWI/SNF protein ATRX are both associated with two intranuclear domains: ND10/PML bodies and heterochromatin [7].
• These results imply that our novel suicide switch system may provide a powerful tool to delineate or identify the signaling molecules for Daxx-mediated apoptotic machinery in B lymphocyte progenitors through JNK activation [11].

Analytical, diagnostic and therapeutic context of Daxx

• However, these protein aggregates are dissociated in cells producing sufficient IE1 through titration of PML, Daxx, and HDAC-2 [13].
• Daxx also forms complexes with RelB while bound to its target sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays and chromatin immunoprecipitation experiments [9].

References