SKN-1 functions in C elegans oxidative stress responses

SKN-1 在秀丽隐杆线虫氧化应激反应中发挥作用

• 批准号: 6885680
• 负责人: RIVA O GARVIN
• 金额: $ 5.75万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-24 至 2006-12-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885680
• 关键词: Caenorhabditis elegans; JUN kinase; RNA interference; acid aminoacid ligase; arsenic; detoxification; developmental genetics; enzyme induction /repression; gene expression profiling; green fluorescent proteins; helminth genetics; microarray technology; oxidative stress; postdoctoral investigator; transcription factor

DESCRIPTION (provided by applicant): Our lab has demonstrated that SKN-1, the transcription factor that specifies the mesoderm fate during early embryogenesis, functions similarly to vertebrate Nrf proteins. SKN-1 accumulates in the intestine nuclei and activates the expression of GCS- 1 in response to different classes of oxidative stress and antioxidants. Besides redox stimuli, SKN-1 is also regulated by GSK-3, DAF-2 and p38 suggesting that this transcription factor might have an essential and global role in the C. elegans oxidant stress defense. In this proposal I will investigate whether arsenite induction of SKN-1 and its target GCS-1 requires also JNK singling and whether sulforaphane induction of SKN-1 and its target GCS-1 requires p38 and/or JNK signaling. I will also identify other genes regulated by SKN-1 using microarrays. And finally, I will investigate whether W02H5.7, an expressed gene highly similar to skn-1, may have parallel or overlapping functions in respect to SKN-1.

描述（由申请人提供）： 我们的实验室已经证明，SKN-1（一种在早期胚胎发生过程中决定中胚层命运的转录因子）的功能与脊椎动物 Nrf 蛋白类似。 SKN-1 在肠细胞核中积聚，并激活 GCS-1 的表达，以响应不同类别的氧化应激和抗氧化剂。除了氧化还原刺激之外，SKN-1 还受到 GSK-3、DAF-2 和 p38 的调节，表明该转录因子可能在秀丽隐杆线虫氧化应激防御中具有重要的全局作用。在本提案中，我将研究亚砷酸盐诱导 SKN-1 及其靶标 GCS-1 是否也需要 JNK 信号转导，以及萝卜硫素诱导 SKN-1 及其靶标 GCS-1 是否需要 p38 和/或 JNK 信号传导。我还将使用微阵列识别 SKN-1 调控的其他基因。最后，我将研究与 skn-1 高度相似的表达基因 W02H5.7 是否可能与 SKN-1 具有平行或重叠的功能。