含有三联基序 (TRIM) 的蛋白质是 RING 型 E3 泛素连接酶最大的亚家族之一，控制重要的生物过程，如细胞凋亡、自噬、信号转导、先天免疫和肿瘤发生。迄今为止，TRIM家族成员之间的相互调节鲜有报道。在这里，我们首次发现肺癌和肾癌细胞中 TRIM21 和 TRIM8 之间存在直接的相互调节，其机制是通过 Lys48 (K48) 连接的泛素化激活蛋白酶体途径。后续研究证实临床非小细胞肺癌（NSCLC）和肾细胞癌（RCC）组织中存在负相关表达，与肿瘤进展密切相关。我们的研究结果强调了 TRIM21 和 TRIM8 之间可能存在的稳态，这可能会影响细胞干性，并有望为癌症治疗提供新思路。© 2023。作者，获得 Springer Nature Limited 的独家许可。

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.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.