ATP1B3, the β3 subunit of the sodium-potassium pump (Na/K-ATP pump), interacts with the α-subunit ATP1A1 to form an essential complex for maintaining cellular homeostasis and membrane potential in all eukaryotic cells [4]. It is also involved in multiple signaling pathways, such as the NF-κB pathway [1,2,3].

In the context of diseases, ATP1B3 has been studied in various models. In glioma cells, knockdown of ATP1B3 via siRNA reduces cell proliferation, migration, and invasion, suggesting its role in promoting these processes through the MAPK/NF-κB signaling pathway [3]. In acute myeloid leukemia (AML), when ATP1B1 (its paralog) is poorly expressed, elimination of ATP1B3 destabilizes the Na/K-ATP pump, leading to cell death, making it a potential therapeutic target [4]. In hepatitis B virus (HBV) studies, overexpression of ATP1B3 in HepG2 cells reduces HBsAg and HBeAg levels, while its silencing promotes their expression. It does so by activating the NF-κB pathway and inducing anti-HBV factors like BST-2 [1]. Additionally, it can reduce HBV envelope proteins through a proteasome-dependent pathway [2].

Overall, ATP1B3 is crucial for maintaining cellular functions related to the sodium-potassium pump. Model-based research, especially knockdown and knockout-like experiments, has revealed its significance in diseases such as glioma, AML, and HBV infection, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Zheng, Baisong, Zhang, Jun, Zheng, Tianhang, Wang, Yingchao, Zhang, Wenyan. 2019. ATP1B3 cooperates with BST-2 to promote hepatitis B virus restriction. In Journal of medical virology, 92, 201-209. doi:10.1002/jmv.25599. https://pubmed.ncbi.nlm.nih.gov/31556466/

2. Zhang, Jun, Zheng, Tianhang, Zhou, Xiaolei, Zheng, Baisong, Zhang, Wenyan. 2021. ATP1B3 Restricts Hepatitis B Virus Replication Via Reducing the Expression of the Envelope Proteins. In Virologica Sinica, 36, 678-691. doi:10.1007/s12250-021-00346-2. https://pubmed.ncbi.nlm.nih.gov/33534085/

3. Yan, Qikang, Sun, Quan, Feng, Yan, Hu, Qingyun, Zhu, Jinling. 2025. ATP1B3 may promote glioma proliferation and migration through MAPK/NF-KB signaling pathway. In Frontiers in oncology, 15, 1537687. doi:10.3389/fonc.2025.1537687. https://pubmed.ncbi.nlm.nih.gov/40027130/

4. Schneider, Constanze, Spaink, Hermes, Alexe, Gabriela, Oellerich, Thomas, Stegmaier, Kimberly. . Targeting the Sodium-Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia. In Cancer research, 84, 3354-3370. doi:10.1158/0008-5472.CAN-23-3560. https://pubmed.ncbi.nlm.nih.gov/39024560/