Api5, also known as Apoptosis Inhibitor 5, is a nuclear protein with diverse functions. It serves as an effective apoptosis inhibitor, though its structure differs from other Inhibitors of Apoptosis Proteins (IAPs). Api5 is involved in multiple pathways, such as FGF2-related signaling which impacts processes like cell survival, cancer stem-cell-like properties, and chemotherapy resistance. It also contributes to E2F1-mediated cell cycle regulation and mRNA nuclear export. Its high expression in many tumors makes it a potential target for cancer treatment [1,4].

In mud crabs, RNAi-mediated knockdown of Api5 led to increased White Spot Syndrome Virus (WSSV) copy numbers and apoptotic rate of hemocytes, highlighting its significance in the immune response [1]. In the Atg16l1-mutant mouse model, viral infection inhibited the secretion of Api5 from γδ IELs, resulting in a loss of Paneth cells and enhanced susceptibility to intestinal injury. Therapeutic administration of recombinant Api5 protected Paneth cells in vivo in mice and ex vivo in human organoids with the ATG16L1 risk allele [2]. In breast cancer cell models, knockdown of Api5 downregulated FGF2 signalling, reducing proliferation and in vivo tumorigenic potential [3]. In cancer cells, RNAi-mediated silencing of API5 restored antigen-specific immune sensitivity, while its introduction into API5(low) cells conferred immune resistance [4]. Also, in cisplatin-resistant cells, API5 acted as a chemo-resistant factor, and inhibition of its downstream FGFR1 reversed cisplatin resistance in vitro and in vivo [5].

In conclusion, Api5 plays essential roles in anti-apoptosis, immune response, cell cycle regulation, and cancer-related processes. Studies using gene-knockdown or knockout models in different organisms, including mouse models, have revealed its significance in diseases such as viral infections, inflammatory bowel diseases, and various cancers. These findings provide valuable insights into potential therapeutic strategies targeting Api5 for treating related diseases.

References:

1. Hu, Hang, Deng, Nan, Zhao, Xinshan, Wei, Weiqian, Gong, Yi. 2023. API5-Hsp20 axis regulate apoptosis and viral infection in mud crab (Scylla paramamosain). In Frontiers in microbiology, 14, 1323382. doi:10.3389/fmicb.2023.1323382. https://pubmed.ncbi.nlm.nih.gov/38143869/

2. Matsuzawa-Ishimoto, Yu, Yao, Xiaomin, Koide, Akiko, Koide, Shohei, Cadwell, Ken. 2022. The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death. In Nature, 610, 547-554. doi:10.1038/s41586-022-05259-y. https://pubmed.ncbi.nlm.nih.gov/36198790/

3. Kuttanamkuzhi, Abhijith, Panda, Debiprasad, Malaviya, Radhika, Gaidhani, Gautami, Lahiri, Mayurika. 2023. Altered expression of anti-apoptotic protein Api5 affects breast tumorigenesis. In BMC cancer, 23, 374. doi:10.1186/s12885-023-10866-7. https://pubmed.ncbi.nlm.nih.gov/37095445/

4. Noh, Kyung Hee, Kim, Seok-Ho, Kim, Jin Hee, Lee, Kyung-Mi, Kim, Tae Woo. 2014. API5 confers tumoral immune escape through FGF2-dependent cell survival pathway. In Cancer research, 74, 3556-66. doi:10.1158/0008-5472.CAN-13-3225. https://pubmed.ncbi.nlm.nih.gov/24769442/

5. Jang, Han Sol, Woo, Seon Rang, Song, Kwon-Ho, Kim, Jae-Hoon, Kim, Tae Woo. 2017. API5 induces cisplatin resistance through FGFR signaling in human cancer cells. In Experimental & molecular medicine, 49, e374. doi:10.1038/emm.2017.130. https://pubmed.ncbi.nlm.nih.gov/28883546/