Hong Yoon Ki, Lee Nam Gon, Lee Min Jung, Park Min Soo, Choi Gahee, Suh Yoon Seak, Han Seung Yeop, Hwang Soojin, Jeong Gilsang, Cho Kyoung Sang
Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
Biochem Biophys Res Commun. 2009 Jun 26;384(2):160-6. doi: 10.1016/j.bbrc.2009.04.112. Epub 2009 May 4.
Mutation of the XNP/ATRX gene, which encodes an SNF2 family ATPase/helicase protein, leads to ATR-X syndrome and several other X-linked mental retardation syndromes. Although XNP/ATRX is a chromatin remodeler, the molecular mechanism by which mental retardation occurs in patients with ATR-X has yet to be determined. To better understand the role of XNP/ATRX in neuronal development, we expressed Drosophila XNP (dXNP/DATRX) ectopically in Drosophila neurons. Neuronal expression of dXNP/DATRX resulted in various developmental defects and induced strong apoptosis. These defects and apoptosis were suppressed by Drosophila inhibitor of apoptosis protein 1. Expression of dXNP/DATRX also increased JNK activity and the levels of reaper and hid transcripts, which are pro-apoptotic factors that activate caspase. Furthermore, dXNP/DATRX-induced rough eye phenotype and apoptosis were suppressed by dFOXO deficiency. These results suggest that dXNP/DATRX is involved in caspase-dependent apoptosis in Drosophila neurons via regulation of the JNK and dFOXO pathway.
编码一种SNF2家族ATP酶/解旋酶蛋白的XNP/ATRX基因突变会导致ATR-X综合征以及其他几种X连锁智力迟钝综合征。尽管XNP/ATRX是一种染色质重塑因子，但ATR-X患者出现智力迟钝的分子机制尚未确定。为了更好地理解XNP/ATRX在神经元发育中的作用，我们在果蝇神经元中异位表达了果蝇XNP（dXNP/DATRX）。dXNP/DATRX的神经元表达导致了各种发育缺陷并诱导了强烈的细胞凋亡。果蝇凋亡抑制蛋白1抑制了这些缺陷和细胞凋亡。dXNP/DATRX的表达还增加了JNK活性以及促凋亡因子收割者（reaper）和hid转录本的水平，这些促凋亡因子可激活半胱天冬酶。此外，dFOXO缺陷抑制了dXNP/DATRX诱导的粗糙眼表型和细胞凋亡。这些结果表明，dXNP/DATRX通过调节JNK和dFOXO途径参与果蝇神经元中依赖半胱天冬酶的细胞凋亡。
