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Endoplasmic reticulum protein 29 (ERp29) is an ER luminal protein that has a role in protein unfolding and secretion, but its role in cancer is unclear. Recently, we reported that overexpression of ERp29 significantly inhibited cell proliferation and prevented tumorigenesis in highly proliferative MDA-MB-231 breast cancer cells. Here, we show that ERp29-induced cancer cell growth arrest is modulated by the interplay between the concomitant phosphorylation of p38 and upregulation of the inhibitor of the interferon-induced, double-stranded RNA-activated protein kinase, p58 IPK . In this cell model, ERp29 overexpression significantly downregulates modulators of cell proliferation, namely urokinase plasminogen activator receptor, b 1 -integrin and epidermal growth factor receptor. Furthermore, ERp29 significantly (Po0.001) increases phosphorylation of p38 (p-p38) and reduces matrix metalloproteinase-9 secretion. The role of ERp29 in upregulating cyclin-dependent kinase inhibitors (p15 and p21) and in downregulating cyclin D 2 is demonstrated in slowly proliferating ERp29-overexpressing MDA-MB-231 cells, whereas the opposite response was observed in ERp29-knockdown MCF-7 cells. Pharmacological inhibition of p-p38 downregulates p15 and p21 and inhibits eIF2a phosphorylation, indicating a role for p-p38 in this process. Furthermore, p58 IPK expression was increased in ERp29-overexpressing MDA-MB-231 cells and highly decreased in ERp29-knockdown MCF-7 cells. This upregulation of p58 IPK by ERp29 suppresses the activation of p-p38/p-PERK/p-eIF2a by repressing eIF2a phosphorylation. In fact, reduction of p58 IPK expression by RNA interference stimulated eIF2a phosphorylation. The repression of eIF2a phosphorylation by p58 IPK prevents ERp29-transfected cells from undergoing ER-dependent apoptosis driven by the activation of ATF4/CHOP/caspase-3. Hence, the interplay between p38 phosphorylation and p58 IPK upregulation has key roles in modulating ERp29-induced cell-growth arrest and survival.

Intercropping can achieve sustainable agricultural development by increasing plant diversity. In this study, we investigated the effects of tomato monoculture and tomato/potato-onion intercropping systems on tomato seedling growth and changes of soil microbial communities in greenhouse conditions. Results showed that the intercropping with potato-onion increased tomato seedling biomass. Compared with monoculture system, the alpha diversity of soil bacterial and fungal communities, beta diversity and abundance of bacterial community were increased in the intercropping system. Nevertheless, the beta-diversity and abundance of fungal community had no difference between the intercropping and monoculture systems. The relative abundances of some taxa (i.e., Acidobacteria-Subgroup-6, Arthrobacter, Bacillus, Pseudomonas) and several OTUs with the potential to promote plant growth were increased, while the relative abundances of some potential plant pathogens (i.e., Cladosporium) were decreased in the intercropping system. Redundancy analysis indicated that bacterial community structure was significantly influenced by soil organic carbon and pH, the fungal community structure was related to changes in soil organic carbon and available phosphorus. Overall, our results suggested that the tomato/potato-onion intercropping system altered soil microbial communities and improved the soil environment, which may be the main factor in promoting tomato growth.