Birc3-KO Mouse

Birc3, also known as cellular IAP2, is a member of the human inhibitors of apoptosis proteins (IAPs) family. Characterized by the presence of baculoviral IAP repeat (BIR) domains involved in protein-protein interactions, it also contains other important domains. Birc3 is involved in multiple cellular processes, such as apoptosis regulation, inflammatory signaling, and immunity. It is associated with the non-canonical NF-κB pathway [1].

In chronic lymphocytic leukemia (CLL), BIRC3 genetic inactivation due to deletions or point mutations is associated with shorter progression-free survival, poor prognosis, and chemoimmunotherapy resistance [1]. In renal ischemia-reperfusion injury, inhibiting Birc3 with AT-406 enhanced apoptosis of kidney tissues, suggesting that its upregulation may protect against this injury [2]. In renal fibrosis, endothelial Birc3 promotes the process through modulating Drp1-mediated mitochondrial fission via the MAPK/PI3K/Akt pathway [3]. In rheumatoid arthritis fibroblast-like synoviocytes, the high expression of BIRC3 promotes cell survival and inflammatory responses, while inhibiting its expression can reduce cytokine secretion and cell proliferation [4]. In asthma, BIRC3 is highly expressed in induced sputum and is positively correlated with eosinophilic and allergic indicators and airway obstruction [5]. In glioblastoma, BIRC3 expression increases with recurrence, and its up-regulation results in apoptosis evasion and therapeutic resistance [6].

In conclusion, Birc3 plays crucial roles in multiple disease conditions, including cancer, kidney diseases, rheumatoid arthritis, and asthma. Studies on Birc3, especially those using gene-knockout or conditional-knockout models (if applicable in the references), have helped to reveal its functions in apoptosis regulation, inflammation, and disease progression, providing potential therapeutic targets for these diseases.

References:

1. Frazzi, Raffaele. 2021. BIRC3 and BIRC5: multi-faceted inhibitors in cancer. In Cell & bioscience, 11, 8. doi:10.1186/s13578-020-00521-0. https://pubmed.ncbi.nlm.nih.gov/33413657/

2. Wang, Sixu, Zhao, Meishan, Zhang, Xiaofei, Tian, Ye, Qiu, Wei. 2023. Birc3 and Tip1 are upregulated in renal ischemia reperfusion injury. In Gene, 876, 147492. doi:10.1016/j.gene.2023.147492. https://pubmed.ncbi.nlm.nih.gov/37209886/

3. Chen, Shuai, He, Qingqing, Yang, Huaiyu, Huang, Hongxing. 2024. Endothelial Birc3 promotes renal fibrosis through modulating Drp1-mediated mitochondrial fission via MAPK/PI3K/Akt pathway. In Biochemical pharmacology, 229, 116477. doi:10.1016/j.bcp.2024.116477. https://pubmed.ncbi.nlm.nih.gov/39128586/

4. Meng, Qingliang, Wei, Kai, Shan, Yu. 2024. E3 ubiquitin ligase gene BIRC3 modulates TNF-induced cell death pathways and promotes aberrant proliferation in rheumatoid arthritis fibroblast-like synoviocytes. In Frontiers in immunology, 15, 1433898. doi:10.3389/fimmu.2024.1433898. https://pubmed.ncbi.nlm.nih.gov/39301019/

5. Du, Lijuan, Xu, Changyi, Zeng, Zhimin, Liang, Yuxia, Guo, Yubiao. 2022. Exploration of induced sputum BIRC3 levels and clinical implications in asthma. In BMC pulmonary medicine, 22, 86. doi:10.1186/s12890-022-01887-2. https://pubmed.ncbi.nlm.nih.gov/35287655/

6. Wang, Dapeng, Berglund, Anders, Kenchappa, Rajappa S, Mulé, James J, Etame, Arnold B. 2016. BIRC3 is a novel driver of therapeutic resistance in Glioblastoma. In Scientific reports, 6, 21710. doi:10.1038/srep21710. https://pubmed.ncbi.nlm.nih.gov/26888114/