Trim28-flox Mouse

TRIM28, also known as tripartite motif protein 28, KAP1 or TIF1β, is an epigenetic co-repressor protein. It mediates transcriptional silencing and participates with Kruppel-associated box domain zinc finger proteins (KRAB-ZFP) in repressing transposable elements (TE) [6]. It also has E3 ubiquitin ligase activity and can promote SUMOylation of substrates. TRIM28 is involved in multiple cellular processes such as DNA damage repair, maintaining cancer cellular stemness, and regulating gene transcription [3].

In cancer, TRIM28 shows complex roles. In gastric cancer, it promotes immune escape by increasing PD-L1 abundance [1]. In non-small cell lung cancer, it promotes anti-PD-1 resistance by enhancing the recruitment of myeloid-derived suppressor cells [7]. However, in Wilms' tumour, TRIM28 acts as a classical tumour suppressor gene, with both alleles generally disrupted in the tumour [2]. In viral infections, TRIM28 promotes porcine epidemic diarrhea virus replication by inhibiting the JAK-STAT1 pathway [5] and enhances SARS-CoV-2 virulence through mediating nucleocapsid protein SUMOylation [4].

In conclusion, TRIM28 has diverse and context-dependent functions. In cancer, it can act as both a tumour promoter and suppressor depending on the cancer type. In viral infections, it promotes viral replication and virulence. Gene knockout and conditional knockout mouse models would be valuable to further understand its role in these biological processes and diseases, providing insights into potential therapeutic strategies.