Background: For unknown reasons, p21 expression induces different effects in cells, including arrest, death, and growth/ prosurvival signals. Results: Cancer cell lines respond with arrest or apoptosis to p21 expression depending on mitochondria sensitivity to oxidants. Conclusion: Cell-specific sensitivity to oxidative stress determines p21-induced cell death.Significance: This provides a rationale to find therapies that up-regulate p21 in cells that are more sensitive to oxidants to favor a death response.
Two proteins comprising the ZEB family of zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and cancer. By studying regulation of their expression, we describe a novel mechanism that limits ZEB2 protein synthesis. A protein motif located at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises protein synthesis. The function of this protein motif is dependent on stretches of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Incorporation of these triplets in the homologous region of ZEB1 does not affect protein translation. Our data suggest that rare codons have a regulatory role only if they are present within appropriate protein structures. We speculate that pools of transfer RNA available for protein translation impact on the configuration of epithelial mesenchymal transition pathways in tumor cells.
In recent years, the advance in whole-genome sequencing technology has changed the study of infectious diseases. The emergence of genome sequencing has improved the understanding of infectious diseases, which has revamped many fields, such as molecular microbiology, epidemiology, infection control, and vaccine production. In this review we discuss the findings of Salmonella enterica serovar Typhi genomes, publicly accessible from the initial complete genome to the recent update of Salmonella enterica serovar Typhi genomes, which has greatly improved Salmonella enterica serovar Typhi and other pathogen genomic research. Significant information on genetic changes, evolution, antimicrobial resistance, virulence, pathogenesis, and investigation from the genome sequencing of S. Typhi is also addressed. This review will gather information on the variation of the Salmonella enterica serovar Typhi genomes and hopefully facilitate our understanding of their genome evolution, dynamics of adaptation, and pathogenesis for the development of the typhoid point-of-care diagnostics, medications, and vaccines.
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