p63和c-Myc都是在细胞周期和肿瘤发生中起重要作用的转录调控因子，目前对二者的交互作用鲜有报道。在前期的研究中，我们发现p63的主要蛋白亚型ΔNp63α能通过其C端与c-Myc的抑制因子MM1直接结合，并促进MM1的蛋白酶体降解，从而解除其对c-Myc的抑制，进而调节细胞周期。这是我们发现的一种新的对c-Myc的调控方式。在本项目中，我们将对这种调控分子机理进行更深入的研究：1.阐明ΔNp63α转录因子活性对于其促进MM1蛋白降解的影响；2.阐明ΔNp63α对c-Myc蛋白稳定性和mRNA水平的影响；3.筛选介导ΔNp63α促进MM1降解途径的蛋白因子；4.研究ΔNp63α/MM1/c-Myc通路在细胞增殖、细胞存活和细胞衰老中的作用。我们的研究对于阐明p63如何调节c-Myc及其在肿瘤发生中的作用具有重要意义，并有可能对以此通路作为肿瘤治疗靶点提供理论依据

Both p63 and c-Myc are important transcription factors playing key roles in cell cycle and tumorigenesis, but crosstalk between them is rarely documented. Our preliminary data demonstrates a novel regulation of c-Myc by p63: ΔNp63α, the predominant protein isoform of p63 gene, directly binds to MM1, which is an inhibitory factor of c-Myc, via its C terminus, and facilitates proteasomal degradation of MM1, consequently leading to depression of MM1-mediated supression of c-Myc, and resulting in modulation on cell cycle. In this project, we are further investigating this regulation, focusing on: 1. effects of ΔNp63α transactivity on its function of MM1 degradation; 2. effects of ΔNp63α on stability and mRNA level of c-Myc; 3. screening of protein factors required for ΔNp63α-facilitated proteasomal degradation of MM1; 4. effects of ΔNp63α/MM1/c-Myc pathway on cell proliferation, cell survival and cell senescence. Our research on the ΔNp63α/MM1/c-Myc pathway is helpful to define the mechanism how p63 regulates c-Myc and its roles in tumorigenesis, likely providing a theoretical basis for therapies targetting this pathway.