Browsing by Subject "Physiological adaptation"

Now showing 1 - 2 of 2
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    Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress
    (Cold Spring Harbor Laboratory Press, 2018-12-12) Wek, Ronald C.; Biochemistry and Molecular Biology, School of Medicine
    A central mechanism regulating translation initiation in response to environmental stress involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways that help to restore protein homeostasis. Coincident with repression of protein synthesis, many gene transcripts involved in the stress response are not affected or are even preferentially translated in response to increased eIF2α phosphorylation by mechanisms involving upstream open reading frames (uORFs). This review highlights the mechanisms regulating eIF2α kinases, the role that uORFs play in translational control, and the impact that alteration of eIF2α phosphorylation by gene mutations or small molecule inhibitors can have on health and disease.
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    Stress response pathways in protozoan parasites
    (Wiley, 2008) Vonlaufen, Nathalie; Kanzok, Stefan M.; Wek, Ronald C.; Sullivan, William J., Jr.; Pharmacology and Toxicology, School of Medicine
    Diseases caused by protozoan parasites have a dramatic impact on world health. Emerging drug resistance and a general lack of experimental understanding has created a void in the medicine cabinet used to treat these widespread infections. A novel therapeutic idea that is receiving more attention is centred on targeting the microbe's response to the multitude of environmental stresses it encounters. Protozoan pathogens have complex life cycles, often having to transition from one host to another, or survive in a cyst form in the environment until a new host arrives. The need to respond to environmental cues and stress, and endure in less than optimal conditions, is paramount to their viability and successful progression through their life cycle. This review summarizes the research on parasitic stress responses for Apicomplexa, kinetoplastids and anaerobic protozoa, with an eye towards how these processes may be exploited therapeutically.