Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers

Characterization of early autophagy signaling by quantitative phosphoproteomics

“…A direct comparison with this study is challenging as both, resveratrol and spermidine, target the acetylation machinery, and thus function most likely by different signaling routes than starvation and rapamycin. 55 Nevertheless, it is interesting to note that in agreement with this study we also identified regulation of the most apparent kinase motifs identified by Bennetzen et al, 62 namely RxxS and SP motifs. Recently, the MTOR-responsive phosphoproteome has been the focus of at least 3 studies focusing on the role of MTOR in cancer and growth factor signaling.…”

“…60,61 Thus, we hypothesized that phosphorylation would be important in the earliest steps after induction and focused on the events happening within the first half-hour of treatment. Nevertheless, it is clear that phosphorylation continues to play a role throughout the process of autophagy exemplified by a recent study by Bennetzen et al 62 that applied a similar experimental setup to characterize the phosphorylation response after 2 h treatment, 62 focusing on events taking place after the first wave of phosphorylation signaling. In this study autophagy was induced by treating cells with the compounds resveratrol or spermidine.…”

Molecular Basis of the ‘Anti-Aging' Effect of Spermidine and Other Natural Polyamines - A Mini-Review

“…Autophagy genes have been shown to be targets for Foxo [22], the downstream effector of the insulin-like signalling (IIS) pathway, indisputably involved in aging and lifespan regulation. Furthermore, spermidine decreases the phosphorylation status of PKB/Akt in HCT116 cells [21] and of Akt in LPS-activated BV2 microglial cells [10]. It will be interesting to study whether the effect of spermidine on lifespan overlaps with the IIS pathway.…”

“…CK2 could act as a sensor for polyamine levels and translate the information to the MAPK pathway. Furthermore, some MAPKs show altered phosphorylation status upon spermidine treatment in HTC116 cells [21] and MAPKs phosphorylation is reduced by spermidine in LPS-activated BV2 microglial cells [10]. In tomato green fruits exposed to spermidine (1 m M for 30 min) at high temperature, spermidine upregulates MAPK family genes [25] suggesting more involvement of polyamines with the MAPK pathway.…”

“…Spermidine triggered a general hypoacetylation, which will likely induce gene expression changes [3]. Spermidine treatment changed the phosphorylation status of many kinases [7] and activated several phosphatases [21] in human colon carcinoma HCT116 cells, potentially regulating many signalling pathways. A lot of the anti-aging effects of spermidine seem to involve autophagy and pathways that will lead to the induction of autophagy are likely targets for the mechanisms of action of spermidine.…”