Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability
Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability
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DOI：
10.1038/sj.onc.1205877
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发表时间：
2002-09-05
期刊：
影响因子：
8
通讯作者：
Feinstein, E
中科院分区：
文献类型：
--
作者：
Budanov, AV;Shoshani, T;Feinstein, E
cDNA微阵列杂交被用来试图确定新的基因参与细胞对长时间缺氧的反应。其中一个新基因命名为Hi 95，与p53调控的GADD家族成员PA 26具有显著的同源性。除了其诱导响应于长时间缺氧，增加Hi 95转录后观察到的DNA损伤或氧化应激，但不高温或血清饥饿。尽管通过长时间缺氧或通过氧化应激诱导Hi 95最可能是p53非依赖性的，但其响应于DNA损伤处理（γ-或UV-照射，或多柔比星）的诱导以p53依赖性方式发生。发现Hi 95全长cDNA的过表达对于许多类型的培养细胞是有毒的，直接导致它们的凋亡性死亡或对血清饥饿和DNA损伤处理敏感。出乎意料的是，在MCF 7-tet-off细胞中Hi 95 cDNA的条件性过表达导致其对缺氧/葡萄糖剥夺或H2 O2诱导的细胞死亡的保护。因此，Hi 95基因似乎参与响应于不同应激条件的细胞活力的复杂调节。
cDNA microarray hybridization was used in an attempt to identify novel genes participating in cellular responses to prolonged hypoxia. One of the identified novel genes, designated Hi95 shared significant homology to a p53-regulated GADD family member PA26. In addition to its induction in response to prolonged hypoxia, the increased Hi95 transcription was observed following DNA damage or oxidative stress, but not following hyperthermia or serum starvation. Whereas induction of Hi95 by prolonged hypoxia or by oxidative stress is most likely p53-independent, its induction in response to DNA damaging treatments (gamma- or UV-irradiation, or doxorubicin) occurs in a p53-dependent manner. Overexpression of Hi95 full-length cDNA was found toxic for many types of cultured cells directly leading either to their apoptotic death or to sensitization to serum starvation and DNA damaging treatments. Unexpectedly, conditional overexpression of the Hi95 cDNA in MCF7-tet-off cells resulted in their protection against cell death induced by hypoxia/glucose deprivation or H2O2. Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions.