热激、氧化应激和病原微生物侵入均会使细胞产生应激反应。作为分子伴侣的热休克蛋白介导细胞应激反应的产生，协助细胞抵抗不良刺激侵扰。卵子作为雌性生殖细胞，对外界刺激极为敏感。分子伴侣功能异常将导致卵子不能正常成熟。应激诱导磷酸化蛋白1（STIP1）是一种蛋白伴侣分子。我们的前期结果证实STIP1在小鼠卵子成熟过程中以泛素化形式大量表达。在模拟人体发烧体温40℃热激条件下，STIP1显著地由卵子胞质向核区迁移和聚集。STIP1功能抑制导致细胞骨架形态异常、DNA双链断裂增加、细胞凋亡率升高、卵子成熟失败。通过MALDI和LC-MS双重质谱分析，我们鉴定出一种新的参与STIP1泛素化修饰的分子RNF20。本项目利用超高分辨结合活细胞示踪、功能敲减和补偿、体外泛素化等技术，阐明RNF20参与STIP1泛素化的机理，揭示STIP1在热激条件下对卵子的保护机制，为应激压力导致的人类不孕不育提供理论依据。

Environmental and physiological stresses, including heat shock, oxidative stress and invasion of pathogens, will induce cellular stress response. This response is mediated by heat shock proteins that function as molecular chaperones, assisting cell in resisting harmful stimuli. As female germ cells, oocytes are extremely sensitive to the external stimulation. Abnormal function of molecular chaperone will lead to failure of oocyte maturation. Stress-induced phosphoprotein 1 (STIP1) plays roles as a kind of protein chaperone. Our preliminary results showed that in mouse oocyte, STIP1 expressed abundantly in ubiquitin form. Under the culture condition of 40℃ that mimic the high fever, we observed a significant accumulation of STIP1 from oocyte cytoplasm to nuclei. Functional inhibition of STIP1 lead to morphological abnormalities of cytoskeleton, increased DNA double-strand breaks, oocyte early apoptosis, as well as failure of oocyte maturation. Further, by employing MALDI and LC-MS proteomic approach, we identified a new candidate named RNF20 that probably participate in STIP1 ubiquitin process. This project intends to illustrate the mechanism of RNF20 mediated STIP1 ubiquitin by employing high resolution microscopy, living cell image, functional disturb and rescue approach. This study will uncover the protection mechanism of STIP1 during oocyte maturation in heat shock condition, and provide theoretical basis for stress induced infertility in human.