Ultraviolet (UV) radiation can cause stresses or act as a photoregulatory signal depending on its wavelengths and fluence rates. Although the most harmful effects of UV on living cells are generally attributed to UV-B radiation, UV-A radiation can also affect many aspects of cellular processes. In cyanobacteria, most studies have concentrated on the damaging effect of UV and defense mechanisms to withstand UV stress. However, little is known about the activation mechanism of signaling components or their pathways which are implicated in the process following UV irradiation. Motile cyanobacteria use a very precise negative phototaxis signaling system to move away from high levels of solar radiation, which is an effective escape mechanism to avoid the detrimental effects of UV radiation. Recently, two different UV-A-induced signaling systems for regulating cyanobacterial phototaxis were characterized at the photophysiological and molecular levels. Here, we review the current understanding of the UV-A mediated signaling pathways in the context of the UV-A perception mechanism, early signaling components, and negative phototactic responses. In addition, increasing evidences supporting a role of pterins in response to UV radiation are discussed. We outline the effect of UV-induced cell damage, associated signaling molecules, and programmed cell death under UV-mediated oxidative stress.

We analyzed the effects of inactivating the pteridine glycosyltransferase gene (pgtA) on the photomovement of the cyanobacterium Synechocystis sp. PCC 6803 under different light conditions. The pgtA mutant displayed abnormal photomovement under UV-A/blue light. In particular, the pgtA mutant showed a negative phototactic response under UV-A (315–400 nm), whereas the wild-type did not show any photomovement. Inhibition of pterin biosynthesis by N-acetylserotonin (NAS), an inhibitor of sepiapterin reductase, also inhibited a positive phototactic response of the wild-type under white and blue light. In addition, negative phototaxis of the pgtA mutant was observed under UV-A/blue light in the presence of NAS. These results indicated that the product of the PgtA enzyme, cyanopterin, is involved in the inhibition of the negative phototaxis of the wild-type by sensing the UV-A. However, 2,4-diamino-6-hydroxypyrimidine-mediated inhibition of GTP cyclohydrolase I, the rate-limiting enzyme for pterin biosynthesis, significantly increased the positive phototaxis toward UV-A in the wild-type and the pgtA mutant. Furthermore, we measured the action spectrum of phototaxis in vivo for the wild-type and pgtA mutant. Maximal activity of the wild-type was at 300, 380 and 440 nm, indicating absorption by pterins and flavin. In particular, the UV-A/ blue peak at 380 and 440 nm obtained from the action spectrum of phototaxis was found to be closely correlated with the in vitro absorption spectrum previously reported for the cyanobacterial cryptochrome DASH. By investigating the photomovement of the wild-type and pgtA mutant to UV and blue light, we suggest that pterin can function as the chromophore of putative UV/blue photoreceptor(s) in cyanobacterial phototaxis.

Thermococcus onnurineus NA1, a sulfur-reducing hyperthermophilic archaeon, is capable of H₂-producing growth, considered to be hydrogenogenic carboxydotrophy. Utilization of formate as a sole energy source has been well studied in T. onnurineus NA1. However, whether formate can be used as its carbon source remains unknown. To obtain a global view of the metabolic characteristics of H₂-producing growth, a quantitative proteome analysis of T. onnurineus NA1 grown on formate, CO, and starch was performed by combining one-dimensional SDS-PAGE with nano UPLC-MS^E. A total of 587 proteins corresponding to 29.7% of the encoding genes were identified, and the major metabolic pathways (especially energy metabolism) were characterized at the protein level. Expression of glycolytic enzymes was common but more highly induced in starch-grown cells. In contrast, enzymes involved in key steps of the gluconeogenesis and pentose phosphate pathways were strongly up-regulated in formate-grown cells, suggesting that formate could be utilized as a carbon source by T. onnurineus NA1. In accordance with the genomic analysis, comprehensive proteomic analysis also revealed a number of hydrogenase clusters apparently associated with formate metabolism. On the other hand, CODH and CO-induced hydrogenases belonging to the Hyg4-II cluster, as well as sulfhydrogenase-I and Mbx, were prominently expressed during CO culture. Our data suggest that CO can be utilized as a sole energy source for H₂ production via an electron transport mechanism and that CO₂ produced from catabolism or CO oxidation by CODH and CO-induced hydrogenases may subsequently be assimilated into the organic carbon. Overall, proteomic comparison of formate- and CO-grown cells with starch-grown cells revealed that a single carbon compound, such as formate and CO, can be utilized as an efficient substrate to provide cellular carbon and/or energy by T. onnurineus NA1.

Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines. The differential effect of dasatinib was not correlated with the basal SRC activity of each cell line. Moreover, the GC cell lines showing the strong antitumor effects of dasatinib were refractory to other SRC inhibitors, i.e., bosutinib and saracatinib, suggesting that unexpected dasatinib’s targets could exist. To profile the targets of dasatinib in GC, we performed activity-based protein profiling (ABPP) via mass spectrometry using a desthiobiotin-ATP probe. We identified 29 and 18 kinases as potential targets in dasatinib-sensitive (SNU-216, MKN-1) and -resistant (SNU-484, SNU-601) cell lines, respectively. The protein–protein interaction mapping of the differential drug targets in dasatinib-sensitive and -resistant GC using the STRING database suggested that dasatinib could target cellular energy homeostasis in the drug-sensitive GC. RNAi screening for identified targets indicated p90RSK could be a novel dasatinib target, which is important for maintaining the viability and motility of GC cells. Further functional validation of dasatinib off-target actions will provide more effective therapeutic options for GC.