2. Academic Validation
  3. TRAIP suppresses bladder cancer progression by catalyzing K48-linked polyubiquitination of MYC

TRAIP suppresses bladder cancer progression by catalyzing K48-linked polyubiquitination of MYC

  • Oncogene. 2023 Dec 20. doi: 10.1038/s41388-023-02922-0.
Jingtian Yu # 1,  Mingxing Li # 1,  Lingao Ju # 2,  Fenfang Zhou 3,  Yejinpeng Wang 1,  Yi Zhang 4 5,  Renjie Zhang 1,  Wenzhi Du 1 6,  Ruoyu Huang 1,  Kaiyu Qian 1 2,  Gang Wang 1 2,  Yu Xiao 7,  Xinghuan Wang 8 9 10
Affiliations

Affiliations

  • 1 Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 Euler Technology, ZGC Life Sciences Park, Beijing, China.
  • 5 Center for Quantitative Biology, School of Life Sciences, Peking University, Beijing, China.
  • 6 Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
  • 7 Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China. [email protected].
  • 8 Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. [email protected].
  • 9 Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. [email protected].
  • 10 Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China. [email protected].
  • # Contributed equally.
PMID: 38123820 DOI: 10.1038/s41388-023-02922-0
Abstract

TRAF-interacting protein (TRAIP), an E3 ligase containing a RING domain, has emerged as a significant contributor to maintaining genome integrity and is closely associated with Cancer. Our study reveals that TRAIP shows reduced expression in bladder Cancer (BLCA), which correlates with an unfavorable prognosis. In vitro and in vivo, TRAIP inhibits proliferation and migration of BLCA cells. MYC has been identified as a novel target for TRAIP, wherein direct interaction promotes K48-linked polyubiquitination at neighboring K428 and K430 residues, ultimately resulting in proteasome-dependent degradation and downregulation of MYC transcriptional activity. This mechanism effectively impedes the progression of BLCA. Restoring MYC expression reverses suppressed proliferation and migration of BLCA cells induced by TRAIP. Moreover, our results suggest that MYC may bind to the transcriptional start region of TRAIP, thereby exerting regulatory control over TRAIP transcription. Consequently, this interaction establishes a negative feedback loop that regulates MYC expression, preventing excessive levels. Taken together, this study reveals a mechanism that TRAIP inhibits proliferation and migration of BLCA by promoting ubiquitin-mediated degradation of MYC.

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