Phospho-Daxx (S668) Polyclonal Antibody, 100µg, (ATB-P0625)

Description

Background:

This gene encodes a multifunctional protein that resides in multiple locations in the nucleus and in the cytoplasm. It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor erythroblastosis virus E26 oncogene homolog 1. In the nucleus, the encoded protein functions as a potent transcription repressor that binds to sumoylated transcription factors. Its repression can be relieved by the sequestration of this protein into promyelocytic leukemia nuclear bodies or nucleoli. This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate apoptosis. The subcellular localization and function of this protein are modulated by post-translational modifications, including sumoylation, phosphorylation and polyubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activatiopn of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as histone chaperone that facilitates deposition of histone H3.3. Acts as targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upopn neuronal activation asociates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV).

Product datasheet:

Overview
Product Description	Phospho-Daxx (S668) Polyclonal Antibody, 100µg, (ATB-P0625)
Image
Species Reactivities	Human
Immunogen	Synthesized peptide derived from human Daxx around the phosphorylation site of S668.
Properties
Form	Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Storage Instructions	-20°C/1 year
Clonality	Polyclonal

References:

1. Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive. Tang SY, et al. Diagn Pathol, 2014 Jan 8. PMID 24398161 Free PMC Article
2. Berberine represses DAXX gene transcription and induces cancer cell apoptosis. Li J, et al. Lab Invest, 2013 Mar. PMID 23295648 Free PMC Article
3. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. Shalginskikh N, et al. J Virol, 2013 Feb. PMID 23221555 Free PMC Article
4. Dualistic function of Daxx at centromeric and pericentromeric heterochromatin in normal and stress conditions. Morozov VM, et al. Nucleus, 2012 May-Jun. PMID 22572957 Free PMC Article
5. Induction of myelogenous leukemia cells with histone deacetylase inhibitors through down-regulating the Daxx protein expression. Li C, et al. J Huazhong Univ Sci Technolog Med Sci, 2009 Oct. PMID 19821084
6. Daxx, a novel Fas-binding protein that activates JNK and apoptosis.
   Yang X., Khosravi-Far R., Chang H.Y., Baltimore D.
   Cell 89:1067-1076(1997) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
7. Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region.
   Kiriakidou M., Driscoll D.A., Lopez-Guisa J.M., Strauss J.F. III
   DNA Cell Biol. 16:1289-1298(1997) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION. Tissue: Placenta.
8. Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death.
   Pluta A.F., Earnshaw W.C., Goldberg I.G.
   J. Cell Sci. 111:2029-2041(1998) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CENPC, SUBCELLULAR LOCATION. Tissue: Cervix carcinoma.
9. TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense cluster at the centromeric end of the MHC.
   Herberg J.A., Beck S., Trowsdale J.
   J. Mol. Biol. 277:839-857(1998) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
10. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes.
    Li R., Pei H., Watson D.K., Papas T.S.
    Oncogene 19:745-753(2000) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: T-cell.