Phosphomevalonate Kinase Controls β‐Catenin Signaling via the Metabolite 5‐Diphosphomevalonate

• DOI: 10.1002/advs.202204909
• Publication Date: 2023-02-21T17:47:12Z
• Authors: Zhiqiang Chen; Xinyi Zhou; Xiaojun Zhou; Yi Tang; Mingzhu Lu; Jianhong Zhao; Chenhui Tian; Mingzhi Wu; Yanliang Liu; Edward V. Prochownik; Fubing Wang; Youjun Li
• Keywords: Beta-catenin

β-catenin signaling is abnormally activated in cancer. Here, this work screens the mevalonate metabolic pathway enzyme PMVK to stabilize using a human genome-wide library. On one hand, PMVK-produced MVA-5PP competitively binds CKIα prevent Ser45 phosphorylation and degradation. other functions as protein kinase directly phosphorylate Ser184 increase its nuclear localization. This synergistic effect of together promotes signaling. In addition, deletion impairs mouse embryonic development causes lethal. deficiency liver tissue alleviates DEN/CCl