The functions and roles of sestrins in regulating human diseases

Table 1 Structure and functions of human sestrins

Sestrins	Transcript variant	Crystal structure	Regulators	Functions	References
hSesn1	3 (~ 48,55,68 kDa)	Unknown (composed mostly of α-helical regions)	p53, FoXO	① Inhibition of ROS ② Nutrition sensing (amino acid, glucose, leucine) ③ Inhibition of mTORC1 ④ Induction of autophagy	[48, 104, 163, 194]
hSesn2	1 (~ 60 kDa)	Two-fold pseudosymmetry with 3 subdomains	p53, Nrf2, ATF4, C/EBPβ, JNK/c-Jun, AP-1, HIF1	① Inhibition of ROS, DNA damage, and ER stress ② Nutrition sensing (amino acid, glucose, leucine) ③ Inhibition of cell growth and mTORC1 ④ Induction of autophagy ⑤ Maintaining homeostasis of glucose, insulin, fatty acid, and triglyceride	[6, 9, 10, 22, 42, 48, 57, 86, 136, 162, 194]
hSesn3	2 (44,53 kDa)	Unknown	AP-1, FoxO1, FoxO3	① Inhibition of ROS ② Nutrition sensing (amino acid, glucose, and leucine) ③ Regulation of mTORC1/mTORC2/PKB ④ Induction of autophagy ⑤ Maintaining homeostasis of glucose, insulin	[22, 39, 194]

Sesn, Sestrin; Nrf2, nuclear factor erythroid 2-related factor 2; AP-1, activator protein 1; ATF4, activating transcription factor 4; C/EBPβ, CCAAT/enhancer-binding protein beta; JNK, c-Jun N-terminal kinase; HIF1, hypoxia-inducible factor 1; FoxO, forkhead box protein O; ROS, reactive oxygen species; mTORC1, mechanistic target of rapamycin complex 1; mTORC2, mechanistic target of rapamycin complex 2; PKB, protein kinase B, also known as Akt; AMPK, AMP-activated protein kinase

ISSN: 1689-1392