Trim33, also known as TIF-1γ, is a transcriptional repressor and E3 ubiquitin ligase. It is involved in multiple key biological processes and signaling pathways. Trim33 has been implicated in regulating TGF-β/SMAD signaling, and is crucial for dendritic cell differentiation, DNA replication fork progression, and pre-cardiogenic mesoderm development [1,2,4,6]. It also plays a role in the ubiquitination-mediated regulation of proteins, thus influencing various cellular functions. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In the context of disease, haematopoietic-specific Trim33 knockout in mice sensitized them to bleomycin-induced pulmonary fibrosis, suggesting Trim33 is a negative regulator of lung fibrosis [1]. Trim33-deficient mice also showed impaired dendritic cell development, with rapid loss of DC progenitors, pDCs, and cDC1 subset [2]. In prostate cancer, knockdown of TRIM33 sensitized PCa cells to AR antagonists, as TRIM33 drives prostate tumor growth by stabilizing androgen receptor [3]. In multiple myeloma, loss of TRIM33 was associated with genomic instability and increased sensitivity to PARP inhibitors [5].

In conclusion, Trim33 is essential for several biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its significant roles in diseases like pulmonary fibrosis, dendritic cell-related disorders, prostate cancer, and multiple myeloma. Understanding Trim33's functions provides potential therapeutic targets for these diseases.