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Heat shock protein 90 (Hsp90) is a promising cancer drug target as a molecular chaperone critical for stabilization and activation of several of the oncoproteins that drive cancer progression. Its actions depend upon its essential ATPase, an activity fortuitously inhibited with a very high degree of selectivity by natural antibiotics: notably the actinomycete-derived benzoquinone ansamycins (e.g. geldanamycin) and certain fungal-derived resorcyclic acid lactones (e.g. radicicol). The molecular interactions made by these antibiotics when bound within the ADP/ATP-binding site of Hsp90 have served as templates for the development of several synthetic Hsp90 inhibitor drugs. Much attention now focuses on the clinical trials of these drugs. However, because microbes have evolved antibiotics to target Hsp90, it is probable that they often exploit Hsp90 inhibition when interacting with each other and with plants. Fungi known to produce Hsp90 inhibitors include mycoparasitic, as well as plant-pathogenic, endophytic and mycorrhizal species. The Hsp90 chaperone may, therefore, be a prominent target in establishing a number of mycoparasitic (interfungal), fungal pathogen–plant and symbiotic fungus–plant relationships. Furthermore the Hsp90 family proteins of the microbes that produce Hsp90 inhibitor antibiotics are able to reveal how drug resistance can arise by amino acid changes in the highly conserved ADP/ATP-binding site of Hsp90. 相似文献
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R C Fry I J Clarke J T Cummins B M Bindon L R Piper L P Cahill 《Journal of reproduction and fertility》1988,82(2):711-715
Booroola Merino ewes, with (F+; N = 17) and without (++; N = 13) a copy of the fecundity gene were hypophysectomized and 6 weeks later were given an i.m. injection of PMSG (high, medium or low dose) followed by hCG. The induced ovulation rates were observed laparoscopically. Ovulation rates were significantly higher (P less than 0.01) in Booroola F+ ewes than in ++ ewes (8.00 +/- 1.66 s.e.m. vs 3.62 +/- 1.10 respectively). This suggests that the high fecundity of the Booroola ewe may be due primarily to ovarian rather than pituitary factors. 相似文献