Work

WWP1 mediates the ubiquitination and degradation of HIPK3 in bladder cancer cells

Year: 2025

Type: article

Abstract: Protein homeostasis is primarily regulated by post-translational modifications (PTMs). HIPK3 has been recognized as a tumor suppressor across various cancers. However, the impact of PTMs on HIPK3 remains insufficiently explored. This study identified WWP1 as an E3 ubiquitin ligase targeting HIPK3, demonstrating that WWP1 downregulates HIPK3 protein levels by facilitating its ubiquitination. Mechanistically, WWP1 directly interacts with HIPK3, promoting K48-linked polyubiquitination at the K1187 site. The WWP1/HIPK3 axis modulates cancer cell chemosensitivity through the regulation of the JNK signaling pathway. Additionally, Myc was found to act as a transcription factor, enhancing WWP1 expression. These findings offer novel insights into the regulation of HIPK3 at the PTM level.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.108528

Authors: Haichao Chen, Xinyu Na, Pengcheng Hu, Qi Ma, Rui Yu

Institutions: Ningbo University, Ningbo University Affiliated Hospital, Ningbo First Hospital

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430