Thrap3, also known as thyroid hormone receptor-associated protein 3, is involved in multiple biological processes and associated pathways. It participates in transcriptional regulation, interacting with various proteins, and is important for maintaining normal cellular functions, with implications in metabolic regulation, osteogenesis, and genomic stability [1-3]. Gene knockout (KO) and conditional knockout (CKO) mouse models have been valuable in studying Thrap3's functions.

In a high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) model, liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties. Thrap3 deficiency enhanced autophagy and mitochondrial function, and knockout increased the cytosolic translocation and activation of AMPK, indicating its role in NAFLD progression [1]. In the context of osteogenesis, Thrap3 promoted osteoblast differentiation through the Thrap3-Sox9-Runx2 axis by inhibiting the degradation of Runx2 [2]. In cancer cells, Thrap3 interacted with methylated DDX5 to promote R-loop resolution, and its loss increased R-loop accumulation and DNA damage [3].

In conclusion, Thrap3 is crucial in multiple biological processes. KO/CKO mouse models have revealed its role in NAFLD, osteogenesis, and cancer-related genomic stability. Understanding Thrap3 functions provides potential therapeutic targets for diseases such as NAFLD, osteoporosis, and cancer [1-3].

References:

1. Jang, Hyun-Jun, Lee, Yo Han, Dao, Tam, Park, Sung Ho, Choi, Jang Hyun. 2023. Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy. In Experimental & molecular medicine, 55, 1720-1733. doi:10.1038/s12276-023-01047-4. https://pubmed.ncbi.nlm.nih.gov/37524868/

2. Zhou, Lei, Li, Haoran, Sun, Shiwei, Xu, Liang, Wang, Minghai. . Thrap3 promotes osteogenesis by inhibiting the degradation of Runx2. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22231. doi:10.1096/fj.202101706R. https://pubmed.ncbi.nlm.nih.gov/35230719/

3. Kang, Hyun Je, Eom, Hye-Jin, Kim, Hongtae, Kwon, Hyug Moo, Choi, Jang Hyun. 2021. Thrap3 promotes R-loop resolution via interaction with methylated DDX5. In Experimental & molecular medicine, 53, 1602-1611. doi:10.1038/s12276-021-00689-6. https://pubmed.ncbi.nlm.nih.gov/34697388/