WWP1介导膀胱癌细胞中HIPK3的泛素化和降解。

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-04-23 DOI:10.1016/j.jbc.2025.108528

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

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引用次数: 0

摘要

蛋白质稳态主要由翻译后修饰（PTMs）调控。HIPK3已被认为是多种癌症的肿瘤抑制因子。然而，PTMs对HIPK3的影响仍未得到充分探讨。本研究发现WWP1是一种靶向HIPK3的E3泛素连接酶，表明WWP1通过促进HIPK3泛素化而下调其蛋白水平。在机制上，WWP1直接与HIPK3相互作用，促进K1187位点的k48连锁多泛素化。WWP1/HIPK3轴通过调控JNK信号通路调节癌细胞的化学敏感性。此外，Myc被发现作为转录因子，增强WWP1的表达。这些发现为HIPK3在PTM水平的调控提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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.

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来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

期刊介绍： The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.