Wnt/β-catenin信号通路是生物体发育调控及稳态维持的重要通路之一。硫酸软骨素聚合因子CHPF是硫酸软骨素糖链合成所需的糖基转移酶。本项目前期新发现CHPF/Chpf能通过非泛素依赖蛋白酶体途径降解活化的β-catenin，从而负调控Wnt通路并调控斑马鱼胚胎体轴形成。本研究拟结合斑马鱼模型和哺乳动物细胞系，详细分析CHPF/Chpf负调控Wnt/β-catenin信号通路的作用机制，阐明CHPF/Chpf调控胚胎体轴发育的生理作用。预期研究结果1)首次解析CHPF重要的生理功能，丰富对糖基转移酶功能的认识；2)鉴定并阐明Wnt/β-catenin信号通路新调控因子及作用方式，促进对Wnt通路调控网络的认识；3)首次发现活化的β-catenin通过非泛素依赖蛋白酶体途径被降解，为Wnt/β-catenin通路的精细调控提供依据和新视角。

The Wnt/β-catenin signaling pathway plays pivotal roles in embryogenesis of multicellular organisms and adult tissue homeostasis. However，the regulation of β-catenin was not completely clear. Here, we identified Chondroitin Polymerizing Factor (CHPF) played a negative role in Wnt/β-catenin signals. CHPF was a glycosyltransferase which involved in synthesis of the repeating disaccharide region of Chondroitin sulfate chain. The pilot results showed that Chpf regulates body axis formation in zebrafish and promotes the proteasome degradation of active β-catenin by ubiquitin-independent action. To explore the role of Chpf in embryogenesis, we will adapt overexpression, gene knockout, and whole amount in situ hybridization in zebrafish as well as cultured cells to investigate the underlying molecular mechanism of CHPF/Chpf in Wnt/β-catenin signals. The completion of the proposed studies will provide novel insights into the relationship between CHPF/Chpf and Wnt/β-catenin signaling. The anticipated results will lead to understand 1) how Chpf modulates body axis formation in zebrafish embryos and 2) by which mechanism Chpf regulates Wnt/β-catenin signals; 3) the active β-catenin could be modulated by ubiquitin-independent proteasome degradation.