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61.
Intracellular protein levels of p53 and MDM2 have been shown to oscillate in response to ionizing radiation (IR), but the physiological significance of these oscillations remains unclear. The p53-MDM2 negative feedback loop – the putative cause of the oscillations – is embedded in a network involving a mutual antagonism (or positive feedback loop) between p53 and AKT. We have shown earlier that this p53-AKT network predicts an all-or-none switching behavior between a pro-survival cellular state (low p53 and high AKT levels) and a pro-apoptotic state (high p53 and low AKT levels). Here, we show that upon exposure to IR, the p53-AKT network can also reproduce the experimentally observed p53 and MDM2 oscillations. The present work is based on the hypothesis that the physiological significance of the experimentally observed oscillations could be found in their role in regulating the switching behavior of the p53-AKT network between pro-survival and pro-apoptotic states. It is shown here that these oscillations are associated with a significant decrease in the threshold level of IR at which switching from a pro-survival to a pro-apoptotic state occurs. Moreover, oscillations in p53 protein levels induce higher levels of expression of p53-target genes compared to non-oscillatory p53, and thus influence cell-fate decisions between cell cycle arrest/DNA damage repair versus apoptosis. 相似文献
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Trimeric autotransporters require trimerization of the passenger domain for stability and adhesive activity
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In recent years, structural studies have identified a number of bacterial, viral, and eukaryotic adhesive proteins that have a trimeric architecture. The prototype examples in bacteria are the Haemophilus influenzae Hia adhesin and the Yersinia enterocolitica YadA adhesin. Both Hia and YadA are members of the trimeric-autotransporter subfamily and are characterized by an internal passenger domain that harbors adhesive activity and a short C-terminal translocator domain that inserts into the outer membrane and facilitates delivery of the passenger domain to the bacterial surface. In this study, we examined the relationship between trimerization of the Hia and YadA passenger domains and the capacity for adhesive activity. We found that subunit-subunit interactions and stable trimerization are essential for native folding and stability and ultimately for full-level adhesive activity. These results raise the possibility that disruption of the trimeric architecture of trimeric autotransporters, and possibly other trimeric adhesins, may be an effective strategy to eliminate adhesive activity. 相似文献
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Interleukin (IL)-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1) is the lymphoid tissue inducer (LTi)-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome. 相似文献
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Lalitha Ramachandran Kanjoormana Aryan Manu Muthu K. Shanmugam Feng Li Kodappully Sivaraman Siveen Shireen Vali Shweta Kapoor Taher Abbasi Rohit Surana Duane T. Smoot Hassan Ashktorab Patrick Tan Kwang Seok Ahn Chun Wei Yap Alan Prem Kumar Gautam Sethi 《The Journal of biological chemistry》2013,288(26):18777
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Regulation of Bacillus subtilis macrofiber twist development by D-alanine. 总被引:2,自引:1,他引:1
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Twist states of Bacillus subtilis macrofibers were found to vary as a function of the concentration of D-alanine in the medium during growth. L-Alanine in the same concentration range had no effect. Increasing concentrations of D-alanine resulted in structures progressively more right-handed (or less left-handed). All strains examined in this study, including mutants fixed in the left-hand domain as a function of temperature, responded to D-alanine in the same way. All twist states from tight left- to tight right-handedness could be achieved solely by varying the D-alanine concentration. The D-alanine-requiring macrofiber strain 2C8, which carries a genetic defect (dal-1) in the alanine racemase, behaved in a similar fashion. The combined effects of D-alanine and ammonium sulfate (a factor known to influence macrofiber twist development in the leftward direction) were examined by using both strains able to undergo temperature-induced helix hand inversion and others incapable of doing so. In all cases, the effects of D-alanine predominated. A synergism was found in which increasing the concentration of ammonium sulfate in the presence of D-alanine enhanced the right-factor activity of the latter. A D-alanine pulse protocol provided evidence that structures undergo a transient inversion indicative of "memory." Chloramphenicol treatment inhibited the establishment of memory in the D-alanine-induced right to left inversion, supporting the existence of a "left twist protein(s)" that is required for the attainment of left-handed twist states. Chemical analysis of cell walls obtained from right- and left-handed macrofibers produced in the presence and absence of D-alanine, respectively, failed to reveal twist state-specific differences in the overall composition of either peptidoglycan or wall teichoic acids. 相似文献
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Erratum
Structural changes occurring during atreasia in sheep ovarian folliclesMary F. Hay, D.G. Cran and R.M. Moor 相似文献70.
Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. 总被引:55,自引:19,他引:36
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It is widely assumed that degradation of mitotic cyclins causes a decrease in mitotic cdc2/CDC28 kinase activity and thereby triggers the metaphase to anaphase transition. Two observations made on the budding yeast Saccharomyces cerevisiae are inconsistent with this scenario: (i) anaphase occurs in the presence of high levels of kinase in cdc15 mutants and (ii) overproduction of a B-type mitotic cyclin causes arrest not in metaphase as previously reported but in telophase. Kinase destruction is therefore implicated in the exit from mitosis rather than the entry into anaphase. The behaviour of esp1 mutants shows in addition that kinase destruction can occur in the absence of anaphase completion. The execution of anaphase and the destruction of CDC28 kinase activity therefore appear to take place independently of one another. 相似文献