SUMO化修饰对PES1的调控及在乳腺癌发生发展中的作用

The mechanism of gene transcription regulation is always the study hotspot in biology medical field. PES1 which is an estrogen-inducible protein has a high expression in multi-malignancy such as breast cancer, while the regulation mechanism of PES1 and its biology function is not very clear. Especially in molecular mechanism of gene transcription regulation, we know almost no on it. So to know how to regulate the activity of PES1 is a very important tache to reveal the pathogenesis of the malignancy such as breast cancer. Here we have identified that PES1 can be sumoylated that activated its transcriptional activity. So the further study on the SUMOylation of PES1 will contribute to uncover the molecular mechanism of multi-malignancy such as breast cancer, and may supply a new thought and target for prevention and therapy of breast cancer.

基因转录调控的作用机理，一直是生物医学领域的研究热点。PES1是一种雌激素诱导蛋白，已发现在乳腺癌等多种恶性肿瘤中高表达，但对其作用机理及生物学功能仍不十分清楚，特别是在基因转录调控的分子机制方面，对它仍所知甚少，因此弄清PES1的活性是如何被调控的，是弄清乳腺癌等恶性疾病发病机理非常重要的一环。我们初步分析认为SUMO-2能够修饰PES1蛋白而发挥功能性作用，可能对转录起激活作用，因此，进一步的研究，将有助于我们更好地了解乳腺癌等肿瘤发生发展的分子机理，这可能为乳腺癌等恶性肿瘤的预防和治疗提供新的思路和靶标。

肿瘤的发生、发展是遗传因素和环境因素相互作用的结果，雌激素分泌紊乱与多种妇科肿瘤，如乳腺癌、子宫内膜癌等密切相关。雌激素对妇科肿瘤有促进作用，它是通过雌激素受体介导的，本项目拟研究细胞核蛋白PES1的一种重要的翻译后修饰，即SUMO化修饰与雌激素受体ERa及相关协同调节因子间的相互作用，进而探讨细胞核蛋白PES1对雌激素受体介导的基因表达调控，以及在肿瘤发生、发展中的作用。研究不仅可以揭示核受体的基因调控网络，还将有助于阐述雌激素相关生理及病理通路的分子机制，为肿瘤的治疗提供理论依据，为相关疾病的治疗开辟新的思路。