ATF1-T184位点磷酸化在鼻咽癌中的作用及机制研究

活化转录因子ATF1在肿瘤中起着重要作用。我们发现，ATF1第184位Thr位点为其全新磷酸化位点：磷酸化ATF1-T184在鼻咽癌中高表达；该位点突变后，ATF1的转录活性及对鼻咽细胞的转化功能明显改变。推测pATF1-T184在其转录调控及鼻咽癌发生发展中起着重要作用。本课题将深入探讨pATF1-T184在鼻咽癌中的作用及机制：采用免疫组化方法研究pATF1-T184在鼻咽癌中的表达，结合临床以阐明其临床意义；转染ATF1-T184突变体进入鼻咽细胞，观察其克隆形成、成瘤性及转移能力等变化；采用ChIP、IP、报告基因、Western等方法研究ATF1-T184对ATF1的转录调控机制；采用蛋白质免疫共沉淀结合质谱方法（IP-MS）筛选ATF1-T184位点相关的磷酸化激酶并进行各个层面验证。以期阐明pATF1-T184的转录调控机制及在鼻咽癌中的作用，为鼻咽癌诊断和治疗提供新的靶点。

Activating transcription factor 1 (ATF1) played an important role in tumor progression. We found in the pilot study that Thr184 at ATF1 was a novel phosphorylation site at ATF1. Phosphorylated ATF1-T184 was higher in NPC than adjacent tissues. The trascription activity and cell transformation ability on nasopharyngeal carcinoma (NPC ) cells were altered when mutation was implemented at the Thr184. After literature analysis, we could infer that pATF1-T184 played an important role in its transcription regulation and NPC progression. . The biological function and molecular mechanism of pATF1-T184 in NPC progression would be thoroughly investigated in this project: immunohistochemistry staining would be used to investigate the expression status of pATF1-T184 in NPC patients and clinicopathological association would be further analyzed; ATF1-Thr184 mutation transfected NPC cell would be used to investigate ATF1 affecting colony formation, invasion and metastasis; ChIP,IP, luciferase and Western bolt would be used to characterize the transcription regulation of ATF1-T184;IP-MS method would be used to sreen the kinase for pATF1-T184 and the result would be verified by a set of experiments. . This study would strive to elucidate the biological function and transcription regulation of pATF1-T184 in NPC progression, with the hope of finding a new target for NPC diagnosis or therapy.