摘要
Stat3是一个在调控胚胎发育、细胞增殖、凋亡、炎症反应和血管生成等多种生理过程发挥关键作用的重要转录因子。Stat3蛋白有Stat3α和缺少羧基端转录激活结构域的Stat3β两个剪接异构体。Stat3基因纯合缺失突变的小鼠在早期胚胎死亡。表达Stat3β可逆转Stat3纯合缺失突变小鼠的胚胎致死表型,并可诱导其下游基因的短期表达,然而其潜在的转录激活结构域一直没有被测定和证实。为进一步解析Stat3蛋白的结构和功能,本研究构建并在酵母中表达了一系列Stat3蛋白的截短体,利用酵母双杂交和双荧光素酶报告基因实验,在酵母和哺乳动物细胞中证实了Stat3蛋白的第2~11位短肽(aa2-11)具有转录激活的作用。这一发现为表达Stat3β逆转Stat3基因缺失引起小鼠胚胎致死表型提供了一种可能的解释,也进一步加深了对Stat3蛋白结构和功能的了解和认识。
Stat3 is a critical transcription factor involved in regulating embryonic development,cell proliferation,apoptosis,inflammation and angiogenesis.The Stat3 protein exists in two isoforms:the fulllength Stat3αand the truncated Stat3β,which lacks the C-terminal transcriptional activation domain.Homozygous mutations in Stat3 in mice lead to early embryonic lethality,which can be rescued by the expression of Stat3β.To further understand the structure and function of the Stat3 protein,we expressed various truncated versions of Stat3 in yeast and demonstrated that Stat3(aa2-11)could activate transcription in yeast and also function effectively in mammalian cells by performing yeast two-hybrid experiments and dual luciferase assay.Our study offers a potential explanation for how Stat3βexpression can reverse the embryonic lethality observed in Stat3 gene mutant mice and enhances our understanding of the structure and function of the Stat3 protein.
作者
张浩
陶无凡
ZHANG Hao;TAO Wu-fan(Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China;Institute of Developmental Biology and Molecular Medicine,Fudan University,Shanghai 200438,China)
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2024年第5期845-849,共5页
Fudan University Journal of Medical Sciences
基金
国家自然科学基金面上项目(31671330)。
