Daxx-β and Daxx-γ, Two Novel Splice Variants of the Transcriptional Co-repressor Daxx

Wethkamp, Nils; Funke, Sarah; Suschek, Christoph V.; Wetzel, Wiebke; Heikaus, Sebastian; Grinstein, Edgar; Ramp, Uwe; Engers, Rainer; Gabbert, Helmut E.; Mahotka, Csaba

doi:10.1074/jbc.m110.196311

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…The two novel variants of Daxx were termed Daxx-and Daxx-γ, and these variants are generated by alternative splicing. They have a truncated regulatory C terminus, and Daxx-and Daxx-γ show markedly decreased affinities to PML and have a different nuclear distribution [62] . In summary, all three of the prototypical proteins (PML, SP100, and Daxx) of ND10 share some similar characteristics: (1) They colocalize with ND10.…”

Section: Death Domain-associated Proteinmentioning

confidence: 99%

Nuclear domain 10 of the viral aspect

Rivera-Molina

Martínez²,

Tang³

2013

WJV

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Nuclear domain 10 (ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies (PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kDa, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mRNA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix.They are often identified by immunofluorescent assay using specific antibodies against PML, Death domainassociated protein, nuclear dot protein (NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed.

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Section: Death Domain-associated Proteinmentioning

confidence: 99%

Nuclear domain 10 of the viral aspect

Rivera-Molina

Martínez²,

Tang³

2013

WJV

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“…For the Rb proteins, these clearly represent the hypophosphorylated forms of the proteins. For Daxx, it is presently unclear whether faster migrating bands represent different phosphoisoforms or splice variants [89] of the protein.…”

Section: Degradationmentioning

confidence: 99%

Tale of a Tegument Transactivator: The Past, Present and Future of Human CMV pp71

Penkert

Kalejta

2012

Future Virol.

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Herpesviruses assemble large virions capable of delivering to a newly infected cell not only the viral genome, but also viral proteins packaged within the tegument layer between the DNA-containing capsid and the lipid envelope. In this review, we describe the tegument transactivator of the β-herpesvirus human CMV, the pp71 protein. We present the known mechanistic features through which it activates viral gene expression during a lytic infection but fails to do so when the virus establishes latency, and describe how pp71 stimulates the cell cycle and may help infected cells avoid detection by the adaptive immune system. A historical overview of pp71 is extended with current perceptions of its roles during human CMV infections and suggestions for future avenues of experimentation.

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“…38, 39 Several splice variants of Daxx that differ at the C terminus and with regard to their ability to interact with PML have been described. 40 Daxx is a well-established regulator of transcription. Daxx binds to the transcriptional coregulators, CREB-binding protein and histone deacetylase, to DNA methyltransferases 41 as well as to numerous transcription factors, including members of the Pax and p53 families, C/EBPβ, ETS1, SMAD4 and glucocorticoid and androgen receptors.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46

et al. 2013

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The tumor suppressor protein Pdcd4 is a nuclear/cytoplasmic shuttling protein that has been implicated in the development of several types of human cancer. In the nucleus, Pdcd4 affects the transcription of specific genes by modulating the activity of several transcription factors. We have identified the Daxx protein as a novel interaction partner of Pdcd4. Daxx is a scaffold protein with roles in diverse processes, including transcriptional regulation, DNA-damage signaling, apoptosis and chromatin remodeling. We show that the interaction of both proteins is mediated by the N-terminal domain of Pdcd4 and the central part of Daxx, and that binding to Pdcd4 stimulates the degradation of Daxx, presumably by disrupting the interaction of Daxx with the de-ubiquitinylating enzyme Hausp. Daxx has previously been shown to serve as a scaffold for protein kinase Hipk2 and tumor suppressor protein p53 and to stimulate the phosphorylation of p53 at serine 46 (Ser-46) in response to genotoxic stress. We show that Pdcd4 also disrupts the Daxx–Hipk2 interaction and inhibits the phosphorylation of p53. We also show that ultraviolet irradiation decreases the expression of Pdcd4. Taken together, our results support a model in which Pdcd4 serves to suppress the phosphorylation of p53 in the absence of DNA damage, while the suppressive effect of Pdcd4 is abrogated after DNA damage owing to the decrease of Pdcd4. Overall, our data demonstrate that Pdcd4 is a novel modulator of Daxx function and provide evidence for a role of Pdcd4 in restraining p53 activity in unstressed cells.

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Daxx-β and Daxx-γ, Two Novel Splice Variants of the Transcriptional Co-repressor Daxx

Cited by 9 publications

References 41 publications

Nuclear domain 10 of the viral aspect

Nuclear domain 10 of the viral aspect

Tale of a Tegument Transactivator: The Past, Present and Future of Human CMV pp71

Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46

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