WP3664 - Regulation of Wnt / B-catenin signaling by small molecule compounds - Homo sapiens

The Wnt/B-catenin pathway begins with Wnt family activation by MBOAT that allows Wnt proteins to translocate out of a cell and bind to FZD and LRP to form a complex. This complex stimulates B-catenin to bind to the TF/LEF complex to regulate gene expression in the cell. Regulation of this pathway takes place at different levels. The Wnt signaling can be inhibited by DKK3, FZD7, SFRP4, FZD8, V3Nter, and Wnt antibodies or FZD antibodies that inhibit FZD and do not allow formation of FZD/LRP/Wnt complex. Another level of regulation is the destruction complex (TNKS/AXIN/GSK3B/APC/CK1a/CK1e) that is regulated by XAV939, DVL, IC261, and Pyrvinium to catalyze the breakdown of B-catenin, inhibiting its binding to the TCF/LEF complex. Several substances including retinoids, glucocorticoids, and ICG-001 inhibit the TCF/LEF complex to stop Wnt/B-catenin signaling pathways from promoting gene transcription. This pathway is based on figure 4 from White et al.

Proteins on this pathway have targeted assays available via the [CPTAC Assay Portal](https://assays.cancer.gov/available_assays?wp_id=WP3664).

Wnt/β-连环蛋白（Wnt/B-catenin）通路的激活始于膜结合O-酰基转移酶（MBOAT）介导的Wnt家族蛋白活化，该过程使Wnt蛋白能够转运出细胞并结合卷曲蛋白受体（FZD）与低密度脂蛋白受体相关蛋白（LRP），形成复合物。该复合物可促进β-连环蛋白与T细胞因子/淋巴增强因子（TCF/LEF）复合物结合，从而调控细胞内的基因表达。该通路的调控发生在多个层面：Wnt信号可被Dickkopf 3（DKK3）、卷曲蛋白受体7（FZD7）、分泌型卷曲相关蛋白4（SFRP4）、卷曲蛋白受体8（FZD8）、V3Nter以及Wnt抗体或FZD抗体抑制，此类因子可阻断FZD的功能，阻止FZD/LRP/Wnt复合物的形成。另一层调控机制为降解复合物（TNKS/AXIN/GSK3B/APC/CK1α/CK1ε），该复合物可被XAV939、散乱蛋白（DVL）、IC261与吡维铵（Pyrvinium）调控，通过催化β-连环蛋白的降解，抑制其与TCF/LEF复合物的结合。包括类视黄醇、糖皮质激素以及ICG-001在内的多种物质可抑制TCF/LEF复合物，从而阻断Wnt/β-连环蛋白信号通路介导的基因转录。本通路基于White等人发表的图4。

该通路相关蛋白可通过[CPTAC检测门户（CPTAC Assay Portal）](https://assays.cancer.gov/available_assays?wp_id=WP3664)获取靶向检测试剂。