Sesn1, also known as PA26, is a gene with diverse essential functions. It is involved in multiple biological processes such as regulating cell growth, viability, and immune responses. It participates in pathways like the Toll-like receptor (TLR) signaling pathway, CGAS-STING1 signaling pathway, and is associated with mTORC1-related nutrient sensing. It is of great biological importance in areas like skeletal muscle aging, tumor suppression, and immune homeostasis [1,2,3]. Genetic models, especially gene knockout models, have been crucial in studying Sesn1's functions.

In skeletal muscle, knockdown of Sesn1 mimicked the aging phenotypes seen in FOXO3-deficient human myotubes, while its activation alleviated senescence, indicating its role in protecting skeletal muscle from aging [1]. In neuroblastoma, knockdown of Sesn1 promoted cell proliferation, migration, and invasion, and shortened tumor-bearing mice survival time, suggesting it functions as a tumor suppressor gene [2]. In innate immune regulation, Sesn1-deficient mice showed stronger ability against HSV-1 infection, and replenishment of Sesn1 in SLE specimens and trex1 KO mouse model effectively suppressed IFN-I production and autoimmune responses, revealing its role in maintaining immune homeostasis [3].

In conclusion, Sesn1 is a multifunctional gene. Model-based research, especially KO mouse models, has revealed its importance in counteracting skeletal muscle aging, suppressing tumors like neuroblastoma, and maintaining immune homeostasis. These findings contribute to understanding the mechanisms of related diseases and may provide potential diagnostic and therapeutic targets.

References:

1. Jing, Ying, Zuo, Yuesheng, Sun, Liang, Liu, Guang-Hui, Wang, Si. 2023. SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing. In Cell proliferation, 56, e13455. doi:10.1111/cpr.13455. https://pubmed.ncbi.nlm.nih.gov/37199024/

2. Hua, Zhongyan, Chen, Bo, Gong, Baocheng, Ma, Yifan, Li, Zhijie. . SESN1 functions as a new tumor suppressor gene via Toll-like receptor signaling pathway in neuroblastoma. In CNS neuroscience & therapeutics, 30, e14664. doi:10.1111/cns.14664. https://pubmed.ncbi.nlm.nih.gov/38516781/

3. Xu, Lingxiao, Zhang, Hongqian, Qiu, Zuocheng, Wan, Qianya, Pan, Mingyu. 2025. SESN1 negatively regulates STING1 to maintain innate immune homeostasis. In Autophagy, , 1-18. doi:10.1080/15548627.2025.2463148. https://pubmed.ncbi.nlm.nih.gov/39945079/