Emp2, encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family, is a cell-surface protein consisting of approximately 160 amino acids. It has been implicated in regulating cell proliferation, migration, and stemness, and is involved in multiple biological processes such as melanogenesis, hematopoiesis, and cardiogenic differentiation. It may also participate in signaling pathways like mTOR-S6K-ERK1/2 and TGFβ/SMAD/SP1, highlighting its overall biological importance [1,2,4,5].

In knockout models, loss of Emp2 in zebrafish impaired the specification of hemangioblasts and hematopoietic stem and progenitor cells, hematopoiesis, and angiogenesis by increasing the phosphorylation of ERK1/2, suggesting its crucial role in circulation system development [2]. In mouse embryonic stem cells, disruption of Emp2 led to up-regulation of pluripotency markers, delayed mesoderm formation, and compromised cardiogenic differentiation [5]. In MNT1 melanoma cells, Emp2 knockdown decreased the expression of TRP-2 and TYR, inhibiting melanogenesis, as well as reducing cell migration and invasion [3].

Overall, Emp2 is involved in a variety of biological functions including cell differentiation, development, and pigmentation. Gene knockout models in zebrafish and mice have been instrumental in revealing its role in circulation system development, cardiogenic differentiation, and melanoma-related processes, providing insights into potential disease mechanisms and therapeutic targets [2,3,5].

References:

1. Mozaffari, Khashayar, Mekonnen, Mahlet, Harary, Maya, Wadehra, Madhuri, Yang, Isaac. 2022. Epithelial membrane protein 2 (EMP2): A systematic review of its implications in pathogenesis. In Acta histochemica, 125, 151976. doi:10.1016/j.acthis.2022.151976. https://pubmed.ncbi.nlm.nih.gov/36455339/

2. Yang, Zhongcheng, Guo, Di, Zhao, Jinyan, Ke, Tie, Wang, Qing K. 2023. Aggf1 Specifies Hemangioblasts at the Top of Regulatory Hierarchy via Npas4l and mTOR-S6K-Emp2-ERK Signaling. In Arteriosclerosis, thrombosis, and vascular biology, 43, 2348-2368. doi:10.1161/ATVBAHA.123.318818. https://pubmed.ncbi.nlm.nih.gov/37881938/

3. Enkhtaivan, Enkhmend, Kim, Hyun Ji, Kim, Boram, Lee, Ai Young, Lee, Chang Hoon. . Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2. In Biomolecules & therapeutics, 30, 203-211. doi:10.4062/biomolther.2022.001. https://pubmed.ncbi.nlm.nih.gov/35221300/

4. Li, Chien-Feng, Chan, Ti-Chun, Pan, Cheng-Tang, Shiao, Meng-Shin, Shiue, Yow-Ling. 2021. EMP2 induces cytostasis and apoptosis via the TGFβ/SMAD/SP1 axis and recruitment of P2RX7 in urinary bladder urothelial carcinoma. In Cellular oncology (Dordrecht, Netherlands), 44, 1133-1150. doi:10.1007/s13402-021-00624-x. https://pubmed.ncbi.nlm.nih.gov/34339014/

5. Liu, Yang, Dakou, Eleni, Meng, Ying, Leyns, Luc. 2019. Loss of Emp2 compromises cardiogenic differentiation in mouse embryonic stem cells. In Biochemical and biophysical research communications, 511, 173-178. doi:10.1016/j.bbrc.2019.02.048. https://pubmed.ncbi.nlm.nih.gov/30773261/