Fbxo28-KO Mouse

Fbxo28, a member of F-box proteins, serves as the substrate receptor of SCF (SKP1, CULLIN1, F-box protein) ubiquitin ligase complexes. It is involved in multiple biological processes, such as the regulation of protein degradation via the ubiquitin-proteasome system, which impacts various cellular functions and is associated with pathways related to cell division, migration, and metabolism [1,2,3,4,5,6,7]. Genetic models, like gene knockout in mice, can be valuable for studying its functions.

In mouse oocytes, depletion of Fbxo28 via morpholino oligonucleotides injection disrupted spindle morphology and migration during meiosis I, affecting asymmetric division, and this was rescued by exogenous Fbxo28-myc mRNA [2]. In hepatocellular carcinoma (HCC), FBXO28 acts as a negative regulator of migration, invasion, and metastasis. It binds to SNAI2 and promotes its degradation in a PKA-dependent manner, and low FBXO28 expression is linked to poor prognosis of HCC patients [1]. In pancreatic cancer, FBXO28 is highly expressed, promotes cell proliferation, invasion, and metastasis both in vitro and in vivo by regulating SMARCC2 ubiquitination, and high expression is negatively correlated with patient survival prognosis [3]. In hyperlipidemia mouse models, upregulation of FBXO28 alleviated abnormal lipid metabolism and inflammatory responses, reducing high-fat diet-induced hyperlipidemia by promoting RAB27A ubiquitinated degradation [5]. In ovarian cancer, higher FBXO28 expression was associated with poor prognosis, and its upregulation promoted cell viability, proliferation, migration, and invasion through activation of the TGF-β1/Smad2/3 signaling pathway [6].

In conclusion, Fbxo28 plays crucial roles in multiple biological processes and disease conditions. Studies using mouse models, such as in oocyte development, cancer metastasis, and hyperlipidemia, have revealed its functions in cell division, tumor progression, and lipid metabolism. Understanding Fbxo28 provides insights into the mechanisms of these biological processes and potential therapeutic targets for related diseases.

References:

1. Qiao, Xinran, Lin, Jingyu, Shen, Jiajia, Li, Pengyu, Wang, Zhen. 2023. FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation. In Oncogene, 42, 2878-2891. doi:10.1038/s41388-023-02809-0. https://pubmed.ncbi.nlm.nih.gov/37596321/

2. Chang, Haoya, Huang, Chenyang, Cheng, Siyu, Li, Jian, Wang, Xiaohong. 2024. Fbxo28 is essential for spindle migration and morphology during mouse oocyte meiosis I. In International journal of biological macromolecules, 275, 133232. doi:10.1016/j.ijbiomac.2024.133232. https://pubmed.ncbi.nlm.nih.gov/38960234/

3. Liu, Songbai, Liu, Peng, Zhu, Changhao, Wang, Xing, Pan, Yaozhen. 2023. FBXO28 promotes proliferation, invasion, and metastasis of pancreatic cancer cells through regulation of SMARCC2 ubiquitination. In Aging, 15, 5381-5398. doi:10.18632/aging.204780. https://pubmed.ncbi.nlm.nih.gov/37348029/

4. Cai, Lili, Liu, Liang, Li, Lihui, Jia, Lijun. 2019. SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation. In Cellular signalling, 65, 109440. doi:10.1016/j.cellsig.2019.109440. https://pubmed.ncbi.nlm.nih.gov/31678254/

5. Sun, J, Du, B, Chen, M, Wang, X, Hong, J. 2024. FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses. In Journal of endocrinological investigation, 47, 2757-2774. doi:10.1007/s40618-024-02376-5. https://pubmed.ncbi.nlm.nih.gov/38696123/

6. Song, Gendi, Sun, Zhengwei, Chu, Man, Wang, Zhiwei, Zhu, Xueqiong. 2024. FBXO28 promotes cell proliferation, migration and invasion via upregulation of the TGF-beta1/SMAD2/3 signaling pathway in ovarian cancer. In BMC cancer, 24, 122. doi:10.1186/s12885-024-11893-8. https://pubmed.ncbi.nlm.nih.gov/38267923/

7. Phillips, Emma, Balss, Jörg, Bethke, Frederic, Fendt, Sarah-Maria, Goidts, Violaine. 2022. PFKFB4 interacts with FBXO28 to promote HIF-1α signaling in glioblastoma. In Oncogenesis, 11, 57. doi:10.1038/s41389-022-00433-3. https://pubmed.ncbi.nlm.nih.gov/36115843/