Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Post Box No. 1982, Dammam 31441, Saudi Arabia.
Pharmacol Res. 2021 Mar;165:105443. doi: 10.1016/j.phrs.2021.105443. Epub 2021 Jan 27.
Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in innate immunity, systemic lupus erythematosus and Sjögren's syndrome. In addition, TRIM21 involvement in cancer proliferation has been observed. However, the clinical significance of TRIM21 and its role in cancer cell proliferation and suppression remains elusive. Here we discuss the effects of TRIM21 on major cancer promoting proteins such as NF-κB, STAT3, BCL2, p53, p27 and Snail, comparing its signaling pathways under normal conditions and in the presence of a variety of carcinogenesis effectors (oncogenic, genotoxic and UV irradiation). Depending on the cancer type and the carcinogenesis effector, TRIM21 may enhance cancer proliferation, or alternatively it may increase the ubiquitination of many cancer-triggering proteins, resulting in their proteasomal degradation. This indicates the importance of TRIM21 in cancer proliferation and/or apoptosis and suggests its potential as a novel cancer therapeutic target.
三结构域蛋白 21(TRIM21)已知参与固有免疫、系统性红斑狼疮和干燥综合征。此外,还观察到 TRIM21 参与癌症增殖。然而,TRIM21 的临床意义及其在癌细胞增殖和抑制中的作用仍不清楚。在这里,我们讨论了 TRIM21 对主要的癌症促进蛋白(如 NF-κB、STAT3、BCL2、p53、p27 和 Snail)的影响,比较了其在正常条件下和存在各种致癌效应物(致癌、遗传毒性和紫外线照射)时的信号通路。根据癌症类型和致癌效应物,TRIM21 可能会促进癌症增殖,或者它可能会增加许多引发癌症的蛋白质的泛素化,导致它们被蛋白酶体降解。这表明 TRIM21 在癌症增殖和/或细胞凋亡中的重要性,并暗示其作为一种新的癌症治疗靶标的潜力。