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Cell Death Differ., 24 February 2025 | https://doi.org/10.1038/s41418-025-01463-1
Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53
Zhihui Tan 1,2,6, Hyun Min Ko 1,6, Parnian Naji 3, Rong Zhu 1,4, Jieqiong Wang 1, Shibo Huang 1,5, Yiwei Zhang 1, Shelya X. Zeng 1,* and Hua Lu 1,*
1Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA.
2Department of Gynecology, Xiang-Ya Hospital, Central South University, Changsha 410008, China.
3Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
4School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.
5The Research Center for Clinical Trials, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China.
2Department of Gynecology, Xiang-Ya Hospital, Central South University, Changsha 410008, China.
3Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
4School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.
5The Research Center for Clinical Trials, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, China.
6These authors contributed equally: Zhihui Tan, Hyun Min Ko.
*Corresponding authors: correspondence to Shelya X. Zeng or Hua Lu
Abstract
Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2’s C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-27)
- 국외 연구진
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