Sestrin-1 (SESN1)

Sestrin-1 (SESN1) is an intracellular stress-inducible protein encoded by the SESN1 gene and belongs to the sestrin family. It is transcriptionally activated by the tumor suppressor p53 in response to DNA damage and oxidative stress, and functions as a metabolic regulator and antioxidant defense protein. Sestrin-1 inhibits mTORC1 signaling through interaction with the GATOR complex, serving as a leucine sensor and controlling cell growth, autophagy, and cellular metabolism. It also assists in regeneration of peroxiredoxins, reducing reactive oxygen species levels. SESN1 plays a pivotal role in adaptation to genotoxic and oxidative stresses and is implicated in diseases including cancer, metabolic disorders, and radiation sensitivity. Drugs such as cisplatin and doxorubicin upregulate SESN1 expression as part of the cellular stress response, but no targeted therapies are currently approved. SESN1 expression can serve as a biomarker for cellular stress and DNA damage, and its modulation represents both a therapeutic opportunity and risk due to its fundamental role in cell survival and metabolic homeostasis.

Other names

Sestrin 1SESN1PA26SEST1p53-regulated protein PA26p53 activated gene 26p53 regulated PA26 nuclear protein1110002G11Rik

Drugs induce SESN1 expression to modulate *response to cellular stress* (mainly DNA damage, oxidative stress). Inhibition of mTOR pathway via upregulation of SESN1 leads to reduced cell growth and increased autophagy (not directly targeted by drugs - indirect effects mostly).