Figure 1. SESN2 is activated by glucose starvation in manner correlated with the induction of the unfolded protein response.

(a,b) Energetic stress, but not AICAR treatment stimulates SESN2 expression. H1299 cells were treated with glucose-free medium in the presence or absence of pyruvate, rotenone (20 μM), 2-deoxyglucose (2DG) (2.5 mM) or Aicar (1 mM) for 12 hr. The phosphorylation of the components of the AMPK-mTORC1 pathway and the expression of Sestrin family members were analyzed by immunoblotting with the indicated antibodies (a) or quantitative real time PCR (qPCR) (b). The data represent a mean of three independent experiments ± S.D. (b) statistical analysis: one-way ANOVA followed by comparisons to the control group with Bonferroni correction (adjusted α = 0.05/5 = 0.01, **P < 0.01). (c) Energetic stress, but not Aicar treatment, stimulates Sesn2 expression in MEF. MEF were treated and analyzed as in (a). (d–f) Activation of SESN2 correlates with activation of the UPR proteins. H1299 cells were incubated with glucose-free medium for different time intervals and expression of SESN2 and the UPR proteins and phosphorylation of components of the AMPK-mTORC1 pathway were analyzed by immunoblotting (d,e) and qPCR (f).