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Updated: Jun 1, 2025

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
Published on: May 10, 2022
TRIM47 promotes head and neck squamous cell carcinoma malignant progression by degrading XAF1 through ubiquitination
Changyun Yu1, Chen Zhang1, Qianqian Zhang1
1Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Abstract:
Tripartite motif-containing 47 (TRIM47) is a member of the TRIM family, which has E3 ligase activity and has been demonstrated to be involved in tumor development. In this work, we found that TRIM47 is highly expressed in head and neck squamous cell carcinomas (HNSCC) tissues. TRIM47 overexpression promoted HNSCC cell proliferation. Downregulation of TRIM47 suppressed HNSCC cell proliferation and promoted apoptosis and autophagy. TRIM47 suppression caused cell proliferation inhibition and apoptosis promotion could be reversed by 3-MA, an autophagy inhibitor. In mechanism, TRIM47 interacted with XIAP-associated factor 1 (XAF1), promoting its ubiquitination and degradation. XAF1 promoted HNSCC cell apoptosis and autophagy. TRIM47 overexpression caused cell proliferation promotion and autophagy inhibition could be reversed by XAF1 overexpression. Animal experiments confirmed that the knockdown of TRIM47 inhibits tumor growth in vivo. Ultimately, TRIM47 promotes the ubiquitination and degradation of XAF1 and suppresses apoptosis and autophagy to promote the progression of HNSCC.
Insights
Tripartite motif-containing 47 (TRIM47) promotes head and neck squamous cell carcinoma (HNSCC) progression by degrading XAF1, inhibiting apoptosis and autophagy. TRIM47 suppression halts HNSCC growth, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tripartite motif-containing 47 (TRIM47) is an E3 ligase implicated in tumor development.
- TRIM47 is frequently overexpressed in various cancers, suggesting a role in tumorigenesis.
Purpose of the Study:
- To investigate the role of TRIM47 in head and neck squamous cell carcinoma (HNSCC).
- To elucidate the molecular mechanisms by which TRIM47 influences HNSCC progression.
Main Methods:
- Quantitative analysis of TRIM47 expression in HNSCC tissues.
- Cell proliferation, apoptosis, and autophagy assays in HNSCC cell lines with TRIM47 manipulation.
- Co-immunoprecipitation and Western blotting to study protein interactions and degradation.
- In vivo tumor xenograft models in animals.
Main Results:
- TRIM47 is highly expressed in HNSCC tissues and promotes HNSCC cell proliferation.
- TRIM47 downregulation inhibits proliferation, induces apoptosis, and promotes autophagy, effects partially reversible by autophagy inhibition.
- TRIM47 interacts with XIAP-associated factor 1 (XAF1), promoting its ubiquitination and degradation.
- XAF1 overexpression reverses TRIM47-induced proliferation and autophagy inhibition.
- TRIM47 knockdown inhibits tumor growth in vivo.
Conclusions:
- TRIM47 promotes HNSCC progression by mediating the ubiquitination and degradation of XAF1.
- This interaction suppresses apoptosis and autophagy, contributing to tumor development.
- TRIM47 represents a potential therapeutic target for HNSCC treatment.
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