dXNP, a <i>Drosophila</i> homolog of XNP/ATRX, induces apoptosis via Jun‐N‐terminal kinase activation

Lee, Nam Gon; Hong, Yong Deog; Yu, Si Young; Han, Sang-Jae; Geum, Dongho; Cho, Kyoung Sang

doi:10.1016/j.febslet.2007.05.005

Cited by 19 publications

(18 citation statements)

References 28 publications

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“…Moreover, overexpression of ATRX/dXNP exacerbated eye degeneration in the HD fly. 22,23 In contrast, our results show that, in part, the deformations within the fly egg and the degeneration of fly eyes are associated with mtHtt, and the pathological phenomena are mediated by gain of function of ATRX. Despite our demonstration of linking ATRX to the pathogenesis of HD via the formation of heterochromatin condensation and PML-NBs formation, the identification of ATRX targets in HD remains to be determined with a high priority.…”

Section: Discussioncontrasting

confidence: 75%

“…The double expression of ATRX/dXNP exacerbated mtHtt (127Q)-mediated degeneration with complete loss of eye pigmentation. 22,23 Flies that only overexpressed ATRX/dXNP resulted in no significant loss of eye pigmentation and minor disruption in the regular array of ommatidia (Figure 5d). …”

Section: Resultsmentioning

confidence: 99%

“…27 The EP635 flies were also described previously. 22,23 By imprecise excision of a Pelement in the EP635 line, we generated XNP C1 , which has deletion of 1065 bp, removing the first exon, including the translational start site of ATRX/XNP.…”

Section: Methodsmentioning

confidence: 99%

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ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

et al. 2012

Cell Death Differ

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Aberrant chromatin remodeling is involved in the pathogenesis of Huntington's disease (HD) but the mechanism is not known. Herein, we report that mutant huntingtin (mtHtt) induces the transcription of alpha thalassemia/mental retardation X linked (ATRX), an ATPase/helicase and SWI/SNF-like chromatin remodeling protein via Cdx-2 activation. ATRX expression was elevated in both a cell line model and transgenic model of HD, and Cdx-2 occupancy of the ATRX promoter was increased in HD. Induction of ATRX expanded the size of promyelocytic leukemia nuclear body (PML-NB) and increased trimethylation of H3K9 (H3K9me3) and condensation of pericentromeric heterochromatin, while knockdown of ATRX decreased PML-NB and H3K9me3 levels. Knockdown of ATRX/dXNP improved the hatch rate of fly embryos expressing mtHtt (Q127). ATRX/dXNP overexpression exacerbated eye degeneration of eye-specific mtHtt (Q127) expressing flies. Our findings suggest that transcriptional alteration of ATRX by mtHtt is involved in pericentromeric heterochromatin condensation and contributes to the pathogenesis of HD.

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Section: Discussioncontrasting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

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ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

et al. 2012

Cell Death Differ

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“…2A and B), despite the strong apoptosis induced by dXNP, as previously reported ( Fig. 2A, Lee et al, 2007). Furthermore, co-expression of DIAP1, a caspase inhibitor, failed to rescue the malformation phenotype of the xbp1 gene silenced tissue (Fig.…”

Section: Xbp1 Gene Silencing Induces Defects In Developing Tissuessupporting

confidence: 70%

Interference in xbp1 gene expression induces defective cell differentiation and sensory organ development in Drosophila

et al. 2010

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The X-box binding protein 1 (Xbp1) is a transcription factor that is important in the unfolded protein response to protect cells from endoplasmic reticulum (ER) stress and is implicated in several other biological processes, including liver growth and B lymphocyte differentiation. Although the cellular function of Xbp1 has been well studied, its developmental role remains to be elucidated. In the present study, we investigated the developmental role of Drosophila xbp1 using an RNAi-mediated gene silencing system. When xbp1 gene expression was specifically interfered with in developing tissues, such as wing and eye during larval growth, the tissues were strongly deformed. Cell death was not observed in these tissues, and this phenotype was not rescued by the overexpression of Drosophila inhibitor of apoptosis protein 1 (DIAP1), a caspase inhibitor, indicating that these developmental defects are not associated with apoptosis. Furthermore, changes were not observed in cell cycle progression and Jun-N-terminal kinase activation in tissues whose xbp1 gene expression was interfered with. Rather, the xbp1 gene silencing resulted in defective cell differentiation and supernumerary of sensory organ precursors. These results suggest the inability of xbp1 gene silencing to induce strong ER stress and the importance of Drosophila Xbp1 in cell fate determination and sensory organ development.

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“…XNP/ATRX encodes an SNF2 family zinc-finger ATPase/helicase protein 240. It has been shown to be involved in DNA methylation,240 chromatin remodeling,241 transcription,242 the cell cycle and apoptosis.…”

Section: Genes Identified In Human Mental Retardation and Shown To Hamentioning

confidence: 99%

Fruit flies and intellectual disability

Bolduc

Tully²

2009

Fly

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Mental retardation-known more commonly nowadays as intellectual disability-is a severe neurological condition affecting up to 3% of the general population. As a result of the analysis of familial cases and recent advances in clinical genetic testing, great strides have been made in our understanding of the genetic etiologies of mental retardation. Nonetheless, no treatment is currently clinically available to patients suffering from intellectual disability. Several animal models have been used in the study of memory and cognition. Established paradigms in Drosophila have recently captured cognitive defects in fly mutants for orthologs of genes involved in human intellectual disability. We review here three protocols designed to understand the molecular genetic basis of learning and memory in Drosophila and the genes identified so far with relation to mental retardation. In addition, we explore the mental retardation genes for which evidence of neuronal dysfunction other than memory has been established in Drosophila. Finally, we summarize the findings in Drosophila for mental retardation genes for which no neuronal information is yet available. All in all, this review illustrates the impressive overlap between genes identified in human mental retardation and genes involved in physiological learning and memory.

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dXNP, a Drosophila homolog of XNP/ATRX, induces apoptosis via Jun‐N‐terminal kinase activation

Cited by 19 publications

References 28 publications

ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease

Interference in xbp1 gene expression induces defective cell differentiation and sensory organ development in Drosophila

Fruit flies and intellectual disability

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