Physical and functional interactions between Daxx and TSG101

Muromoto, Ryuta; Sugiyama, Kenji; Yamamoto, T.; Oritani, Kenji; Shimoda, Kazuya; Matsuda, Tadashi

doi:10.1016/j.bbrc.2004.02.126

Cited by 25 publications

(17 citation statements)

References 34 publications

(50 reference statements)

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“…Daxx also acts as a transcription corepressor of Pax3 and Ets-1, and as an activator or repressor of Pax5 [31,32,33]. We also found that Daxx forms a functional complex composed of DNA methyltransferase 1, DNA methyltransferase 1 associated protein, and tumor susceptibility gene 101 [34,35]. Although Daxx makes important contributions to apoptosis and has the ability to modulate transcription, many mechanistic aspects of Daxx-function are still unclear.…”

Section: Daxx and Crk In Ifn-systemsmentioning

confidence: 88%

IFN-? limitin: a member of type I IFN with mild lympho-myelosuppression

Oritani

Kanakura

2005

J Cellular Mol Med

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Interferon (IFN)‐ζlimitin has been considered as a novel type I IFN by the Nomenclature Committee of the International Society for Interferon and Cytokine Research. IFN‐ζlimitin shows some sequence homology with IFN‐α and IFN‐β, has a globular structure with five α‐helices and four loops, and recognizes IFN‐α/β receptor. Although IFN‐ζlimitin displays antiviral, immunomodulatory, and antitumor effects, it has much less lymphomyelosuppressive activities than IFN‐α. Treatment of cells with type I IFNs induces and/or activates a number of molecules, which regulate cell cycle and apoptosis. It is noteworthy that IFN‐ζlimitin activates the Tyk2‐Daxx and Tyk2‐Crk pathways weaker than IFN‐α. Because experiments using antisense oligonucleotides have revealed their essential role in type I IFN‐related suppression of lympho‐hematopoiesis, little ability of IFN‐ζlimitin to activate the Tyk2‐dependent signaling pathway may explain its uniquely narrow range of biological activities. Further analysis of structure‐function relationship of type I IFNs will establish an engineered cytokine with useful features of IFN‐ζlimitin.

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Section: Daxx and Crk In Ifn-systemsmentioning

confidence: 88%

IFN-? limitin: a member of type I IFN with mild lympho-myelosuppression

Oritani

Kanakura

2005

J Cellular Mol Med

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“…However, the mechanism by which DAXX binds to sumoylated PML and sumoylated transcription factors is still largely unclear. As DAXX associates directly with a number of DNA binding transcription factors, including Pax3 and Pax5 (36,37), ETS1 (38), p53 (39), and its family members p73 and p63 (45), glucocorticoid receptor (46), androgen receptor (47), and Smad4 (48), it is likely that it represents a crucial link between DNA binding factors and transcriptional regulatory complexes. DAXX-mediated transcriptional repression is due to interaction with HDAC (40), and indeed the SPT domain of DAXX recruits histone deacetylases leading to inactive chromatin structure and transcriptional repression.…”

Section: Hsr/card Domain Of Aire Interacts With Ser/pro/thr-richmentioning

confidence: 99%

DAXX Is a New AIRE-interacting Protein

Meloni

Fiorillo

Corda

et al. 2010

Journal of Biological Chemistry

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The AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in the AIRE gene cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population. To this day, the precise function of the AIRE protein in regulating transcription and its interacting proteins has yet to be entirely clarified. The knowledge of novel AIRE interactors and their precise role will improve our knowledge of its biological activity and address some of the foremost autoimmunity-related questions. In this study, we have used a yeast two-hybrid system to identify AIRE-interacting proteins. This approach led us to the discovery of a new AIRE-interacting protein called DAXX. The protein is known to be a multifunctional adaptor with functions both in apoptosis and in transcription regulation pathways. The interaction between AIRE and DAXX has been validated by in vivo coimmunoprecipitation analysis and colocalization study in mammalian cells. The interaction has been further confirmed by showing in transactivation assays that DAXX exerts a strong repressive role on the transcriptional activity of AIRE.

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“…In addition, Daxx binds to the transcriptional activating factors such as Ets and Pax family proteins and inhibits their transcriptional activities leading to the downregulation of their target genes (Hollenbach et al, 1999;Li et al, 2000b). We also found that Daxx forms a functional complex composed of DNA methyltransferase 1, DNA methyltransferase 1 associated protein, and tumor susceptibility gene 101 (Muromoto et al, 2004a(Muromoto et al, , 2004b.…”

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confidence: 71%

Physical and functional interactions between Daxx and STAT3

et al. 2005

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Signal transducer and activator of transcription 3 (STAT3) play key roles in the intracellular signaling pathways of the interleukin (IL)-6 family of cytokines, which exhibit a diverse set of cellular responses, including cell proliferation and differentiation. Dysregulated IL-6/ STAT3 signaling is involved in the pathogenesis of several diseases, for example autoimmune diseases and tumors. Type I interferon (IFN) induces the expression of proapoptotic genes and has been used in the clinical treatment of several tumors. In the present study, we found that type I IFN suppressed IL-6/STAT3-mediated transcription and gene expression. Furthermore, a type I IFN-induced protein, Daxx, also suppressed STAT3-mediated transcriptional activation, while overexpression of Daxx inhibited IL-6/STAT3-mediated gene expression. Importantly, small-interfering RNA-mediated reduction of Daxx expression enhanced IL-6/leukemia inhibitory factor (LIF)-induced STAT3-dependent transcription. Co-immunoprecipitation studies revealed a physical interaction between Daxx and STAT3 in transiently transfected 293T cells. We further found that Daxx and STAT3 were co-localized in the nucleus. These results indicate that Daxx may serve as a transcriptional regulator of type I IFN-mediated suppression of the IL-6/ STAT3 signaling pathway.

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Physical and functional interactions between Daxx and TSG101

Abstract: ABSTRACT

Cited by 25 publications

References 34 publications

IFN-? limitin: a member of type I IFN with mild lympho-myelosuppression

IFN-? limitin: a member of type I IFN with mild lympho-myelosuppression

DAXX Is a New AIRE-interacting Protein

Physical and functional interactions between Daxx and STAT3

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