Bbc3, also known as BCL2 binding component 3 or PUMA, is a pro-apoptotic gene [1,2,4,5,6,7]. It plays a significant role in the regulation of apoptosis, a programmed cell-death process, and is associated with the intrinsic apoptosis pathway [6]. Genetic models, such as gene knockout mouse models, are valuable for studying its functions.

In a mouse miscarriage model, knockdown of murine Bbc3 efficiently suppressed placental apoptosis and alleviated miscarriage, indicating its role in trophoblast cell apoptosis and miscarriage [1]. In neurons exposed to the organophosphate pesticide chlorpyrifos, Bbc3 loss attenuated CPF-driven neurotoxicity, induction of other apoptosis-related genes, and cleavage of apoptosis executors [3]. In a mouse model of silicosis, Bbc3 knockout mice showed decreased levels of autophagy and fibrosis progression, suggesting Bbc3 in macrophages promotes pulmonary fibrosis development through inducing autophagy during silicosis [4].

In conclusion, Bbc3 is a key regulator in apoptosis and is involved in multiple disease-related biological processes. Gene knockout mouse models have revealed its importance in conditions like miscarriage, neurotoxicity due to pesticide exposure, and silicosis-induced pulmonary fibrosis, providing insights into potential therapeutic targets for these diseases.

References:

1. Zhao, Jingsong, Xu, Zhongyan, Xie, Jiayu, Guo, Jiarong, Zhang, Huidong. 2024. The novel lnc-HZ12 suppresses autophagy degradation of BBC3 by preventing its interactions with HSPA8 to induce trophoblast cell apoptosis. In Autophagy, 20, 2255-2274. doi:10.1080/15548627.2024.2362122. https://pubmed.ncbi.nlm.nih.gov/38836496/

2. Lee, Tzu-Lin, Shen, Wen-Chi, Chen, Ya-Chun, Lee, Chiang-Wen, Chen, Yuh-Lien. 2024. Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. In Autophagy, 21, 374-393. doi:10.1080/15548627.2024.2395799. https://pubmed.ncbi.nlm.nih.gov/39245438/

3. Anderson, Faith L, von Herrmann, Katharine M, Young, Alison L, Havrda, Matthew C. . Bbc3 Loss Enhances Survival and Protein Clearance in Neurons Exposed to the Organophosphate Pesticide Chlorpyrifos. In Toxicological sciences : an official journal of the Society of Toxicology, 183, 378-392. doi:10.1093/toxsci/kfab090. https://pubmed.ncbi.nlm.nih.gov/34289071/

4. Liu, Haijun, Cheng, Yusi, Yang, Jian, Chao, Jie, Liao, Hong. 2017. BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis. In Cell death & disease, 8, e2657. doi:10.1038/cddis.2017.78. https://pubmed.ncbi.nlm.nih.gov/28277537/

5. Zhang, Yuan, Shen, Kai, Bai, Ying, Hu, Gang, Yao, Honghong. 2016. Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity. In Autophagy, 12, 1538-59. doi:10.1080/15548627.2016.1191723. https://pubmed.ncbi.nlm.nih.gov/27464000/

6. da Silva, Matheus Felipe, de Lima, Luan Vitor Alves, Zanetti, Thalita Alves, Lirio Rondina, Débora Berbel, Mantovani, Mário Sérgio. 2022. Diosgenin increases BBC3 expression in HepG2/C3A cells and alters cell communication in a 3D spheroid model. In Mutation research. Genetic toxicology and environmental mutagenesis, 879-880, 503512. doi:10.1016/j.mrgentox.2022.503512. https://pubmed.ncbi.nlm.nih.gov/35914860/

7. Xie, Wei, Zhang, Lei, Jiao, Haifeng, Han, Jiahuai, You, Han. . Chaperone-mediated autophagy prevents apoptosis by degrading BBC3/PUMA. In Autophagy, 11, 1623-35. doi:10.1080/15548627.2015.1075688. https://pubmed.ncbi.nlm.nih.gov/26212789/