64 research outputs found

    Differential recognition of canonical NF-κB dimers by Importin α3

    Get PDF
    Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling

    Ambient Stress vis-a-vis Enzyme Regulators of Carbohydrate Metabolism in Marwari goat from arid tracts in India

    No full text
    The study was designed to determine modulation of enzyme regulators of carbohydrate metabolism in Marwari breed of goat of both sexes and varying age groups during moderate, extreme hot and cold ambiences. The enzyme regulators included sorbitol dehydrogenase (SDH), malate dehydrogenase (MDH), glucose-6-phosphatase (G-6-Pase) and glucose-6-phosphate dehydrogenase (G-6-PDH)which were determined in the serum. The moderate ambience was considered as control for each enzyme regulator and the mean values in UL-1 were 8.67±0.005, 40.87±0.32, 8.04±0.003 and 7.53±0.005, respectively. The mean values of SDH, MDH and G-6-Pase were significantly (p≤0.05) higher during hot and cold ambiences in comparison to respective moderate mean value. However, the increase was more in cold than hot ambience for each case. The mean value of G-6-PDH was significantly (p≤0.05) higher during cold ambience while significantly (p≤0.05) lower during hot ambience in comparison to moderate mean value. In each ambience the sex and age effects were significant (p≤ 0.05) on each enzyme regulators. It could be concluded that extreme ambiences produced modulations in the metabolic reactions reflected on the basis of pattern of variations of enzyme regulators in the seru
    • …
    corecore