Ubap2l, also known as NICE-4, is a ubiquitin-and RNA-binding protein highly conserved in metazoans. It is involved in multiple cellular processes such as cell cycle regulation, stem cell activity, stress-response signaling, and is crucial for maintaining cell homeostasis and survival. It also plays a role in pathways related to the assembly of nuclear pore complexes (NPCs), mitosis, and the formation of stress granules (SGs) and processing bodies (PBs). In addition, it has oncogenic properties in several human cancers [1].

Depletion of Ubap2l in human cells leads to severe mitotic defects as it controls both the localization and protein stability of PLK1, an important mitotic regulator [2]. In gastric cancer, knockdown of Ubap2l impedes cell migration and invasion, while overexpression enhances these abilities, indicating its role in cancer metastasis through the PI3K/AKT/SP1/NF-κB axis [3]. Without Ubap2l (as an SG nucleator), dsRNA triggers excessive inflammation and immune-mediated apoptosis, suggesting its role in the controlled activation of RLR signaling [4].

In conclusion, Ubap2l is essential for various cellular functions including cell cycle, stress response, and NPC homeostasis. Its role in cancer metastasis and immune response control, as revealed through loss-of-function studies, highlights its potential as a therapeutic target, especially in gastric cancer. Understanding Ubap2l through such model-based research contributes to our knowledge of disease mechanisms and may offer new treatment strategies.

References:

1. Guerber, Lucile, Pangou, Evanthia, Sumara, Izabela. 2022. Ubiquitin Binding Protein 2-Like (UBAP2L): is it so NICE After All? In Frontiers in cell and developmental biology, 10, 931115. doi:10.3389/fcell.2022.931115. https://pubmed.ncbi.nlm.nih.gov/35794863/

2. Guerber, Lucile, Vuidel, Aurore, Liao, Yongrong, Sumara, Izabela, Pangou, Evanthia. 2023. UBAP2L-dependent coupling of PLK1 localization and stability during mitosis. In EMBO reports, 24, e56241. doi:10.15252/embr.202256241. https://pubmed.ncbi.nlm.nih.gov/37039032/

3. Li, Ou, Zhao, Cheng, Zhang, Jian, Shu, Yi-Jun, Dong, Ping. 2022. UBAP2L promotes gastric cancer metastasis by activating NF-κB through PI3K/AKT pathway. In Cell death discovery, 8, 123. doi:10.1038/s41420-022-00916-7. https://pubmed.ncbi.nlm.nih.gov/35304439/

4. Paget, Max, Cadena, Cristhian, Ahmad, Sadeem, Mu, Xin, Hur, Sun. . Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA. In Molecular cell, 83, 1180-1196.e8. doi:10.1016/j.molcel.2023.03.010. https://pubmed.ncbi.nlm.nih.gov/37028415/