Mi Zhang, Xindong Shui, Xiaoqing Zheng, Jong Eun Lee, Yingxue Mei, Ruomeng Li, Yuan Tian, Xiuzhi Zheng, Quling Wang, Long Wang, Dongmei Chen, Tao Zhang, Byeong Mo Kim, Jungho Kim, Tae Ho Lee
Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression...
October 7, 2023: Archives of Pharmacal Research