我们既往的研究证实组织蛋白酶L（cathepsin L，CTSL）在辐射抗性及肿瘤侵袭迁移中发挥重要作用，但实现这一作用的具体机制仍不清楚。最近我们发现p53基因热点突变的肿瘤细胞CTSL基础水平低表达可能与启动子甲基化以及转录辅助因子p300的表达缺失相关，电离辐射（IR）通过上调转录因子Egr-1，促进突变p53招募p300并形成复合体，参与CTSL基因的转录调控，提示CTSL的表达可能与p53基因突变密切相关。本课题拟围绕IR对突变p53上调CTSL这一核心科学问题，研究p53基因不同热点突变与CTSL表达的关系，证实Egr-1/p300是IR影响突变p53上调CTSL的重要靶点，揭示p300介导的表观遗传学机制在CTSL基因转录调控中的表现，力求阐明突变p53/Egr-1/p300多靶标蛋白相互作用调控CTSL的分子机制，最终确立CTSL是突变p53功能获得的重要参与者。

Our previous researches showed cathepsin L (CTSL) plays an important role in radiation-resistance and invasion as well as migration of tumor cells，but the mechanism still remains unclear. We recently find that the CTSL expression level of mutant p53 type tumor cells is possibly regulated by methylation status of CTSL promoter and may be correlated with absence of transcriptional coactivator p300. Our recent data show that Egr-1 increases after exposure to ionizing radiation（IR）and induces expression of p300 as well as promotes the formation of mut-p53/p300 complex，and thus regulates expression of CTSL. These findings reveal a correlation between CTSL expression and p53 mutation. Therefore, our plan is to study the relationship between p53 mutation and expression of CTSL and to verify the role of Egr-1/p300 in this regulating mechanism. And uncover the significance of p300-mediated epigenetic mechanism for transcription and regulation of CTSL. Our final goal is to confirm the key role of CTSL in mutant p53 gain of function.