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Mutual regulation between TRIM21 and TRIM8 via K48-linked ubiquitination

Oncogene volume 42, pages 3708–3718 (2023)Cite this article

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Abstract

Tripartite motif (TRIM)-containing proteins, one of the largest subfamilies of the RING type E3 ubiquitin ligases, control important biological processes such as cell apoptosis, autophagy, signal transduction, innate immunity and tumorigenesis. So far, the mutual regulation between TRIM family members has rarely been reported. Here, we found for the first time that there was a direct mutual regulation between TRIM21 and TRIM8 in lung and renal cancer cells, mechanistically by activating their proteasome pathway via Lys48 (K48)- linked ubiquitination. Subsequent studies verified that negatively correlated expressions existed in clinical non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) tissues, which were closely related to tumor progression. Our findings highlighted a possible homeostasis between TRIM21 and TRIM8 that might possibly affect cell stemness and was expected to provide a new idea for cancer therapy.

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Fig. 1: Negative regulation between TRIM21 and TRIM8 proteins in H1299 and 293T cells.
Fig. 2: Identification of the interaction between TRIM21 and TRIM8.
Fig. 3: TRIM21 catalyzes TRIM8 degradation via K48-linked ubiquitination.
Fig. 4: TRIM8 also catalyzes TRIM21 degradation via K48-linked ubiquitination.
Fig. 5: TRIM21 and TRIM8 mediated degradation are through the ubiquitin-proteasome pathway.
Fig. 6: Negatively correlated expressions of TRIM21 and TRIM8 are related to the tumorigenesis in NSCLC and RCC.
Fig. 7: Broken balance between TRIM21 and TRIM8 might be related to the stemness of lung and renal cells.
Fig. 8: Schematic diagram of a direct mutual regulation between TRIM21 and TRIM8.

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The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

We thank Professor Xiansheng Lu for his help in linguistic revision. This work was supported by the National Natural Science Foundation of China (3120566, 31370794) and the key R&D of the Ministry of Science and Technology of China (2016YFC1309604).

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Authors and Affiliations

  1. Beijing Institute of Basic Medical Sciences, 100850, Beijing, China

    Lin Wang, Hui Li, Aixue Huang, Yuechao Zhao, Can Xiao, Jie Dong, Xuemei Liu & Ningsheng Shao

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NS and XL designed the project and wrote the manuscript. LW performed the experiments and analyzed data. HL, AH, YZ, CX and JD provided the technical support. All authors read and approved the final manuscript.

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Correspondence to Xuemei Liu or Ningsheng Shao.

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Wang, L., Li, H., Huang, A. et al. Mutual regulation between TRIM21 and TRIM8 via K48-linked ubiquitination. Oncogene 42, 3708–3718 (2023). https://doi.org/10.1038/s41388-023-02879-0

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