Gnl3l, also known as Guanine nucleotide-binding protein-like 3-like protein, is an evolutionarily conserved GTP-binding nucleolar protein [2,5,6]. It participates in multiple cellular processes such as cell cycle regulation, and is involved in pathways like AMPK, NF-κB, and ATM/p53 [1,3,4]. Gnl3l plays a significant role in various biological functions, and its dysregulation is associated with the development of several diseases, including cancer and chronic obstructive pulmonary disease (COPD) [1-4]. Genetic models, such as gene knockout or knockdown models, are valuable for studying its functions.

In esophageal cancer cells, Gnl3l overexpression promotes cell viability, proliferation, and autophagy via regulating the AMPK signaling pathway [1]. Silencing Gnl3l in KYSE410 cells leads to opposite phenotypes [1]. In acute myeloid leukemia, Gnl3l acts as a poor prognostic factor, enhancing RELA activity, activating NF-κB, promoting cell proliferation, and resisting apoptosis [4]. In COPD, knockdown of Gnl3l in a CS/LPS-induced mouse model and cigarette smoke extract-induced human bronchial epithelial cells improves pathological features, promotes cell viability, and inhibits inflammation, oxidative stress, and the ATM/p53 pathway [3].

In conclusion, Gnl3l is a crucial protein involved in cell cycle regulation, cell proliferation, autophagy, and inflammation. Model-based research, especially knockdown or knockout studies, has revealed its significant roles in cancer and COPD. Understanding Gnl3l's functions provides potential therapeutic targets for these diseases.

References:

1. He, Weiting, Sun, Fengyao, Li, Wen, Yan, Siyuan, Liu, Changqing. 2023. GNL3L promotes autophagy via regulating AMPK signaling in esophageal cancer cells. In Medical oncology (Northwood, London, England), 41, 29. doi:10.1007/s12032-023-02270-9. https://pubmed.ncbi.nlm.nih.gov/38148364/

2. Liu, Pei, Guo, Wenjia, Su, Ying, Chen, Cheng, Lv, Xiaoyi. 2022. Multi-Omics Analysis of GNL3L Expression, Prognosis, and Immune Value in Pan-Cancer. In Cancers, 14, . doi:10.3390/cancers14194595. https://pubmed.ncbi.nlm.nih.gov/36230520/

3. Cai, Qian, Chen, Sirui, Zhu, Yingqun, Li, Zhe. 2023. Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway. In International journal of chronic obstructive pulmonary disease, 18, 2645-2659. doi:10.2147/COPD.S424431. https://pubmed.ncbi.nlm.nih.gov/38022822/

4. Li, Ji, Wu, Zhimin, Pan, Yipeng, Cong, Yun, Fang, Qingliang. 2024. GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia. In Journal of Cancer, 15, 4072-4080. doi:10.7150/jca.95339. https://pubmed.ncbi.nlm.nih.gov/38947394/

5. Thoompumkal, Indu Jose, Subba Rao, Malireddi Rama Krishna, Kumaraswamy, Anbarasu, Krishnan, Rehna, Mahalingam, Sundarasamy. 2015. GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation. In PloS one, 10, e0135845. doi:10.1371/journal.pone.0135845. https://pubmed.ncbi.nlm.nih.gov/26274615/

6. Yasumoto, Hiroaki, Meng, Lingjun, Lin, Tao, Zhu, Qubo, Tsai, Robert Y L. 2007. GNL3L inhibits activity of estrogen-related receptor gamma by competing for coactivator binding. In Journal of cell science, 120, 2532-43. doi:. https://pubmed.ncbi.nlm.nih.gov/17623774/