Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling, including by modulating the activity of the transcription factors NF-kB, FoxM1 and Hif1α, the translation regulator HuR and the cell cycle regulators p21 and survivin. We also identified a small molecule inhibitor, YM-1, that disrupts Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anti-cancer target.
were no significant differences among white-American girls and Russian girls, and there were no ethnic differences between boys in the prevalence of dieting. WhiteAmerican girls and black-American girls were much more likely to identify being overweight as an important nutritional concern than were Russian girls (odds ratios >lo), and there were no ethnic differences among boys. We conclude that preferences for body size, the prevalence of dieting, and concerns about being overweight were similar in Russian and white-American teens, with the exception of Russian teenaged girls who were less likely than American girls to identify being overweight as an important concern. Overall, weight-related attitudes and behaviors in Russian teenagers were more similar to those of white-American teenagers than those of black-American teenagers.Key words: obesity, black Americans, adolescence, weight loss, body weight
IntroductionIt has been hypothesized that weight-related attitudes and behaviors are influenced by the level of economic development and the associated availability of food. According to this theory, an ideal for thinness develops among affluent cultures whereas a preference for plumpness develops among those threatened with food shortages (4,14,36,40). Although attitudes toward body size and dieting behavior have been studied in the United States and in several other cultures (3,5,13,17,21,24,26-3 1,33,42,48), we know of no studies that have examined these issues in a Russian population. The goals of this study were to describe nutrition and weight-related attitudes and behaviors in Russian adolescents and to contrast them with white-American and black-American adolescents.
The GPA assay has limited potential to be used as a biodosimeter of prolonged irradiation, at least in dose interval up to 2.0 Gy. The TCR assay is likely to have greater potential in estimation of recent radiation exposure than the GPA assay.
W e studied the maternal effect for two enzymes of the pentose cycle, 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD), using a genetic system based on the interaction of Pgd-and Z w -alleles, which inactivate 6PGD and G6PD, respectively. The presence and formation of the enzymes was investigated in those individuals that had not received the corresponding genes from the mother. We revealed maternal forms of the enzymes, detectable up to the pupal stage. The activities of "maternal" 6PGD and G6PD per individual increased 20-fold t o 30-fold from the egg stage t o the 3rd larval instar even in the absence of normal Pgd and Zw genes. Immunologic studies have shown that the increase in 6PGD activity is due t o an accumulation of the maternal form of the enzyme molecules. We revealed a hybrid isozyme resulting from an aggregation of the subunits of isozymes controlled by the genes of the mother and embryo itself. These results indicate that the maternal effect in the case of 6PGD is due to a long-lived stable mRNA transmitted with the egg cytoplasm and translated during the development of Drosophila melanogaster.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.