TRIM21 Promotes Differentiation of Hypopharyngeal Squamous Cell Carcinoma Through Improving Protein Stability by Ubiquitination of Cytoskeleton
10.13865/j.cnki.cjbmb.2021.04.1658
- Author:
Yan-Fang NIU
1
;
Tao YANG
1
;
Fang-Yu CHAI
2
;
Wen-Hui PANG
2
;
Ji-Sheng ZHANG
2
;
Ji-Sheng ZHANG
3
;
Yan-Fang NIU
4
;
Tao YANG
4
Author Information
1. Department of Biochemistry and Molecular Biology, Shanxi Medical University
2. Department of Otolaryngology ‐ Head and Neck Surgery, The Affiliated Hospital of Qingdao University
3. Medical Research Center
4. Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education
- Publication Type:Journal Article
- Keywords:
differentiation;
hypopharyngeal squamous cell carcinoma (HPSCC);
tripartite motif containing 21 (TRIM21);
ubiquitination
- From:
Chinese Journal of Biochemistry and Molecular Biology
2021;37(6):790-797
- CountryChina
- Language:Chinese
-
Abstract:
E3 ubiquitin ligase TRIM21(tripartite motif containing 21) plays an important role in regulating cell biological functions and clinical prognosis as oncogene or tumor suppressor in different types of tumors. However,the biological functions and molecular mechanism of TRIM21 in hypopharyngeal squamous cell carcinoma (HPSCC) are still unclear.Our results showed that TRIM21 is highly expressed in moderately and well differentiated HPSCC, suggesting the role of TRIM21 in tumor differentiation. Overexpression and knockdown of TRIM21 inhibited or promoted cell proliferation and migration. Meanwhile, the expression of differentiation markers including KRT10 (keratin 10), IVL (involucrin) and TGM1 (transglutaminase 1) were increased and decreased upon TRIM21 overexpression or knockdown, respectively. The bioinformatics analysis of TRIM21 interacting protein identified by co-immunoprecipitation combined with mass spectrometry suggested that TRIM21 may be closely related to the regulation of cytoskeleton protein. We further demonstrated that TRIM21 interacted with KRT10. The inhibition of protein synthesis by cycloheximide led to upregulation of KRT10 in TRIM21 overexpressing FaDu cells, and ectopic expression of TRIM21 enhanced the ubiquitination level of KRT10. In summary, our results suggest that TRIM21 may promote the HPSCC differentiation by mediating ubiquitination of cytoskeleton proteins to improve the protein stability.
