Gene Symbol: Sesn2
Description: sestrin 2
Alias: HI95, SEST2, Ses2, sestrin-2
Species: mouse
Products:     Sesn2

Top Publications

  1. Papadia S, Soriano F, Léveillé F, Martel M, Dakin K, Hansen H, et al. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat Neurosci. 2008;11:476-87 pubmed publisher
    ..Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPbeta and AP-1, respectively...
  2. Budanov A, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. 2008;134:451-60 pubmed publisher
    ..Correspondingly, Sestrin2-deficient mice fail to inhibit mTOR signaling upon genotoxic challenge. Sestrin1 and Sestrin2 therefore provide an important link between genotoxic stress, p53 and the mTOR signaling pathway. ..
  3. Lee J, Budanov A, Talukdar S, Park E, Park H, Park H, et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 2012;16:311-21 pubmed publisher
    ..We show that Sestrin2--encoded by the Sesn2 locus, whose expression is induced upon hypernutrition--maintains metabolic homeostasis in liver of obese mice...
  4. Wempe F, De Zolt S, Koli K, Bangsow T, Parajuli N, Dumitrascu R, et al. Inactivation of sestrin 2 induces TGF-beta signaling and partially rescues pulmonary emphysema in a mouse model of COPD. Dis Model Mech. 2010;3:246-53 pubmed publisher
    ..Here, we report that the mutational inactivation of the antioxidant protein sestrin 2 (sesn2) partially rescues the emphysema phenotype of Ltbp4S mice and is associated with activation of the TGF-..
  5. Bae S, Sung S, Oh S, Lim J, Lee S, Park Y, et al. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab. 2013;17:73-84 pubmed publisher
    ..We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the ..
  6. Lee J, Budanov A, Karin M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab. 2013;18:792-801 pubmed publisher
    ..Further investigation of Sestrin function and regulation should provide new insights into age-associated metabolic diseases, such as diabetes, myopathies, and cancer. ..
  7. Meechan D, Tucker E, Maynard T, LaMantia A. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A. 2009;106:16434-45 pubmed publisher
    ..Such developmental disruption may alter cortical circuitry and establish vulnerability for developmental disorders, including schizophrenia and autism. ..
  8. Deng W, Cha J, Yuan J, Haraguchi H, Bartos A, Leishman E, et al. p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing. J Clin Invest. 2016;126:2941-54 pubmed publisher
    ..Together, these results reveal that p53-dependent coordination of AMPK and mTORC1 signaling controls parturition timing and suggest that metformin and resveratrol have therapeutic potential to prevent PTB. ..
  9. Petri A, Ahnfelt Rønne J, Frederiksen K, Edwards D, Madsen D, Serup P, et al. The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice. J Mol Endocrinol. 2006;37:301-16 pubmed
    ..These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of alpha-cell-specific gene expression. ..

More Information


  1. Kim M, Bae S, Ryu J, Kwon Y, Oh J, Kwon J, et al. SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy. 2016;12:1272-91 pubmed publisher
    ..Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, suppresses prolonged NLRP3 inflammasome activation by clearance of damaged ..
  2. Tao R, Xiong X, Liangpunsakul S, Dong X. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes. 2015;64:1211-23 pubmed publisher
    ..These findings suggest that Sesn3 can activate Akt via mTORC2 to regulate hepatic insulin sensitivity and glucose metabolism. ..
  3. Ro S, Semple I, Park H, Park H, Park H, Kim M, et al. Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. FEBS J. 2014;281:3816-27 pubmed publisher
    ..Taken together, this study identifies ULK1 as a new p62 Ser403 kinase and establishes Sestrin2 as a promoter of ULK1-mediated p62 phosphorylation. ..
  4. Barkic M, Crnomarković S, Grabusic K, Bogetić I, Panic L, Tamarut S, et al. The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival. Mol Cell Biol. 2009;29:2489-504 pubmed publisher
    ..Our results imply that activation of a p53-dependent checkpoint mechanism in response to various ribosomal protein deficiencies might also play a role in the pathogenesis of congenital malformations in humans. ..
  5. Ding B, Parmigiani A, Divakaruni A, Archer K, Murphy A, Budanov A. Sestrin2 is induced by glucose starvation via the unfolded protein response and protects cells from non-canonical necroptotic cell death. Sci Rep. 2016;6:22538 pubmed publisher
    ..We propose that Sestrin2 protects cells from glucose starvation-induced cell death via regulation of mitochondrial homeostasis. ..
  6. Hao B, Pan X, Fan Y, Lu L, Qian X, Wang X, et al. Oleanolic acid attenuates liver ischemia reperfusion injury by HO-1/Sesn2 signaling pathway. Hepatobiliary Pancreat Dis Int. 2016;15:519-524 pubmed
    ..Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were measured with quantitative real-time RT-PCR and Western blotting...
  7. Kim J, Ro S, Kim M, Park H, Semple I, Park H, et al. Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci Rep. 2015;5:9502 pubmed publisher
    ..Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity. ..
  8. Zhang C, Sun W, Li J, Xiong B, Frye M, Ding D, et al. Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea. Neuroscience. 2017;361:179-191 pubmed publisher
    b>Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown...
  9. Yang Y, Cuevas S, Yang S, Villar V, Escano C, Asico L, et al. Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of reactive oxygen species production. Hypertension. 2014;64:825-32 pubmed publisher
    ..3-fold) and blood pressure. These results suggest that the D2R, via paraoxonase 2 and sestrin2, keeps normal renal redox balance, which contributes to the maintenance of normal blood pressure. ..
  10. Heidler J, Fysikopoulos A, Wempe F, Seimetz M, Bangsow T, Tomasovic A, et al. Sestrin-2, a repressor of PDGFR? signalling, promotes cigarette-smoke-induced pulmonary emphysema in mice and is upregulated in individuals with COPD. Dis Model Mech. 2013;6:1378-87 pubmed publisher
    ..Here we identify the antioxidant protein sestrin-2 (SESN2) as a repressor of PDGFR? signalling, and PDGFR? signalling as an upstream regulator of alveolar maintenance ..
  11. Forsberg K, Wuttke A, Quadrato G, Chumakov P, Wizenmann A, Di Giovanni S. The tumor suppressor p53 fine-tunes reactive oxygen species levels and neurogenesis via PI3 kinase signaling. J Neurosci. 2013;33:14318-30 pubmed publisher
    ..Our results suggest that p53 fine-tunes endogenous ROS levels to ensure the appropriate timing of neurogenesis in eNPCs. This may also have implications for the generation of tumors of neurodevelopmental origin. ..
  12. Morrison A, Chen L, Wang J, Zhang M, Yang H, Ma Y, et al. Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart. FASEB J. 2015;29:408-17 pubmed publisher
    ..Thus, Sestrin2 plays an important role in cardioprotection against I/R injury, serving as an LKB1-AMPK scaffold to initiate AMPK activation during ischemic insults. ..
  13. Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim Y, Akopiants K, et al. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014;9:1281-91 pubmed
    ..This mechanism is potentially involved in mTORC1 regulation by amino acids, rotenone, and tunicamycin, connecting stress response with mTORC1 inhibition. ..
  14. Park H, Park H, Ro S, Jang I, Semple I, Kim D, et al. Hepatoprotective role of Sestrin2 against chronic ER stress. Nat Commun. 2014;5:4233 pubmed publisher
    ..The Sestrin2-mediated unfolded protein response (UPR) may be a general protective mechanism against ER stress-associated diseases. ..
  15. Essler S, Dehne N, Brüne B. Role of sestrin2 in peroxide signaling in macrophages. FEBS Lett. 2009;583:3531-5 pubmed publisher
    ..We conclude that Sestrin2 plays a role in peroxide defense as a reductase for peroxiredoxins. ..
  16. Quan N, Sun W, Wang L, Chen X, Bogan J, Zhou X, et al. Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism. FASEB J. 2017;31:4153-4167 pubmed publisher
    A novel stress-inducible protein, Sestrin2 (Sesn2), declines in the heart with aging. AMPK has emerged as a pertinent stress-activated kinase that has been shown to have cardioprotective capabilities against myocardial ischemic injury...
  17. Jegal K, Park S, Cho S, Byun S, Ku S, Kim S, et al. Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. Biochim Biophys Acta Mol Cell Res. 2017;1864:1295-1307 pubmed publisher
    ..The present study investigated the role of sestrin 2 (SESN2) on ER stress and sought to elucidate the mechanism responsible for the hepatoprotective effect of SESN2 ..
  18. Crisol B, Lenhare L, Gaspar R, Gaspar R, Muñoz V, da Silva A, et al. The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice. Life Sci. 2018;194:98-103 pubmed publisher
    ..Here, we evaluated the effects of acute and chronic aerobic exercise on Sestrin 1 (Sesn1) and Sesn2 protein contents in the skeletal muscle of mice...
  19. Zeng Y, Chi F, Xing R, Zeng J, Gao S, Chen J, et al. Sestrin2 protects the myocardium against radiation-induced damage. Radiat Environ Biophys. 2016;55:195-202 pubmed publisher
    ..Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. ..
  20. Kallenborn Gerhardt W, Lu R, Syhr K, Heidler J, von Melchner H, Geisslinger G, et al. Antioxidant activity of sestrin 2 controls neuropathic pain after peripheral nerve injury. Antioxid Redox Signal. 2013;19:2013-23 pubmed publisher
    ..In the present study, we tested whether the stress-responsive antioxidant protein Sestrin 2 (Sesn2) blocks the ROS-induced neuropathic pain processing in vivo...
  21. Li H, Liu S, Yuan H, Niu Y, Fu L. Sestrin 2 induces autophagy and attenuates insulin resistance by regulating AMPK signaling in C2C12 myotubes. Exp Cell Res. 2017;354:18-24 pubmed publisher
    ..Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes...
  22. Kim M, Yang J, Kim K, Jang C, Jung J, Cho I, et al. Regulation of Toll-like receptor-mediated Sestrin2 induction by AP-1, Nrf2, and the ubiquitin-proteasome system in macrophages. Toxicol Sci. 2015;144:425-35 pubmed publisher
    The Sestrin2 (Sesn2) is an evolutionary conserved enzyme that scavenges reactive oxygen species and regulates autophagy through the AMPK-mTOR pathway...
  23. Peng M, Yin N, Li M. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell. 2014;159:122-133 pubmed publisher
    ..These findings reveal a nonredundant mechanism by which the Sestrin family of GDIs regulates the nutrient-sensing Rag GTPases to control mTORC1 signaling. ..