Lap3, or leucine aminopeptidase 3, is an M1 member of leucine aminopeptidases, which catalyze the hydrolysis of leucine residues [2,3]. It is involved in protein metabolism and may play a role in pathways related to cell growth, autophagy, and amino acid metabolism [2-4, 10].

In bovine mammary epithelial cells, IFN-γ stimulation leads to arginine depletion and malignant transformation, with Lap3 downregulating arginine levels by interfering with ASS1 and promoting cell cycle-related protein expressions, suggesting its role in breast cancer development [1]. In non-alcoholic fatty liver disease (NAFLD), cholesterol-induced upregulation of Lap3 inhibits autophagy in hepatocytes, and Lap3 may serve as a biomarker for NAFLD diagnosis [2]. In glioma cells, high Lap3 expression is correlated with malignancy grade and poor prognosis, and it promotes cell viability, cycle, migration, and invasion [3]. Conversely, in C2C12 myoblasts, Lap3 suppression accelerates myogenic differentiation via the AKT-TFE3 pathway [4]. In sheep embryonic myoblasts, Lap3 expression impacts cell proliferation and myogenic differentiation, and in dairy cattle, its gene polymorphisms are associated with milk production traits and clinical mastitis [5,6]. In sheep and razor clams, LAP3 gene mutations are associated with growth traits [7,8].

In summary, Lap3 is involved in multiple biological processes such as cell proliferation, differentiation, autophagy, and amino acid metabolism, with its dysregulation linked to diseases like breast cancer and NAFLD. Functional studies, including those using potential genetic models like gene knockout, could further clarify its role and offer new therapeutic or breeding strategies.

References:

1. Li, Li, Li, Fengyang, Hu, Xiuhong, Huang, Jing, Lei, Liancheng. 2022. LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells. In BMC cancer, 22, 864. doi:10.1186/s12885-022-09963-w. https://pubmed.ncbi.nlm.nih.gov/35941558/

2. Feng, Lina, Chen, Yanping, Xu, Ke, Lu, Shemin, Li, Dongmin. 2022. Cholesterol-induced leucine aminopeptidase 3 (LAP3) upregulation inhibits cell autophagy in pathogenesis of NAFLD. In Aging, 14, 3259-3275. doi:10.18632/aging.204011. https://pubmed.ncbi.nlm.nih.gov/35404840/

3. He, Xiaojuan, Huang, Qingfeng, Qiu, Xiaojun, Tao, Tao, Wang, Dongling. 2014. LAP3 promotes glioma progression by regulating proliferation, migration and invasion of glioma cells. In International journal of biological macromolecules, 72, 1081-9. doi:10.1016/j.ijbiomac.2014.10.021. https://pubmed.ncbi.nlm.nih.gov/25453285/

4. Osana, Shion, Kitajima, Yasuo, Naoki, Suzuki, Kano, Yutaka, Nagatomi, Ryoichi. 2023. The aminopeptidase LAP3 suppression accelerates myogenic differentiation via the AKT-TFE3 pathway in C2C12 myoblasts. In Journal of cellular physiology, 238, 2103-2119. doi:10.1002/jcp.31070. https://pubmed.ncbi.nlm.nih.gov/37435895/

5. Ge, Ling, Su, Pengwei, Wang, Shan, Yuan, Zehu, Sun, Wei. 2022. New Insight into the Role of the Leucine Aminopeptidase 3 (LAP3) in Cell Proliferation and Myogenic Differentiation in Sheep Embryonic Myoblasts. In Genes, 13, . doi:10.3390/genes13081438. https://pubmed.ncbi.nlm.nih.gov/36011349/

6. Worku, Destaw, Gowane, G R, Mukherjee, Anupama, Joshi, Pooja, Verma, Archana. 2022. Associations between polymorphisms of LAP3 and SIRT1 genes with clinical mastitis and milk production traits in Sahiwal and Karan Fries dairy cattle. In Veterinary medicine and science, 8, 2593-2604. doi:10.1002/vms3.924. https://pubmed.ncbi.nlm.nih.gov/36063537/

7. La, Yongfu, Zhang, Xiaoxue, Li, Fadi, Mo, Futao, Wang, Weimin. 2019. Molecular Characterization and Expression of SPP1, LAP3 and LCORL and Their Association with Growth Traits in Sheep. In Genes, 10, . doi:10.3390/genes10080616. https://pubmed.ncbi.nlm.nih.gov/31416156/

8. Yao, Hanhan, Liu, Chenshan, Lin, Dehai, Lin, Zhihua, Dong, Yinghui. 2019. Polymorphisms of LAP3 gene and their association with the growth traits in the razor clam Sinonovacula constricta. In Molecular biology reports, 47, 1257-1264. doi:10.1007/s11033-019-05231-6. https://pubmed.ncbi.nlm.nih.gov/31853767/