共查询到20条相似文献,搜索用时 15 毫秒
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Tootle TL Silver SJ Davies EL Newman V Latek RR Mills IA Selengut JD Parlikar BE Rebay I 《Nature》2003,426(6964):299-302
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Epac proteins are activated by binding of the second messenger cAMP and then act as guanine nucleotide exchange factors for Rap proteins. The Epac proteins are involved in the regulation of cell adhesion and insulin secretion. Here we have determined the structure of Epac2 in complex with a cAMP analogue (Sp-cAMPS) and RAP1B by X-ray crystallography and single particle electron microscopy. The structure represents the cAMP activated state of the Epac2 protein with the RAP1B protein trapped in the course of the exchange reaction. Comparison with the inactive conformation reveals that cAMP binding causes conformational changes that allow the cyclic nucleotide binding domain to swing from a position blocking the Rap binding site towards a docking site at the Ras exchange motif domain. 相似文献
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SMAD proteins control DROSHA-mediated microRNA maturation 总被引:3,自引:0,他引:3
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Shin J Bossenz M Chung Y Ma H Byron M Taniguchi-Ishigaki N Zhu X Jiao B Hall LL Green MR Jones SN Hermans-Borgmeyer I Lawrence JB Bach I 《Nature》2010,467(7318):977-981
Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI. 相似文献
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New type of POU domain in germ line-specific protein Oct-4. 总被引:72,自引:0,他引:72
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Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product 总被引:49,自引:0,他引:49
THE superfamily of low molecular mass GTP-binding proteins, for which the ras proteins are prototypes, has been implicated in the regulation of diverse biological activities including protein trafficking, secretion, and cell growth and differentiation. One member of this family, CDC42Hs (originally referred to as Gp or G25K), seems to be the human homologue of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc. A second S. cerevisiae protein, CDC24, which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonrandom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product. Here we show that dbl specifically catalyses the dissociation of GDP from CDC42Hs and thereby qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. Although guanine nucleotide exchange activities have been previously described for other members of the Ras-related GTP-binding protein family, this is the first demonstration, to our knowledge, of the involvement of a human oncogenic protein in catalysing exchange activity. 相似文献
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LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription 总被引:4,自引:0,他引:4
Metzger E Wissmann M Yin N Müller JM Schneider R Peters AH Günther T Buettner R Schüle R 《Nature》2005,437(7057):436-439
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The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 总被引:1,自引:0,他引:1
Cloos PA Christensen J Agger K Maiolica A Rappsilber J Antal T Hansen KH Helin K 《Nature》2006,442(7100):307-311
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Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth 总被引:36,自引:0,他引:36