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A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse 总被引:1,自引:0,他引:1
Rosengren Pielberg G Golovko A Sundström E Curik I Lennartsson J Seltenhammer MH Druml T Binns M Fitzsimmons C Lindgren G Sandberg K Baumung R Vetterlein M Strömberg S Grabherr M Wade C Lindblad-Toh K Pontén F Heldin CH Sölkner J Andersson L 《Nature genetics》2008,40(8):1004-1009
In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals. 相似文献
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Residues of the variable region of the T-cell-receptor beta-chain that interact with S. aureus toxin superantigens 总被引:29,自引:0,他引:29
The alpha beta T-cell antigen receptor (TCR) recognizes antigenic peptides in the context of self major histocompatibility complex (MHC) molecules. The specificity of recognition of MHC plus antigen is generally determined by a combination of the variable elements of alpha- and beta-chains of the TCR. Several types of antigen, however, have been identified that, when bound to MHC molecules, stimulate T cells bearing particular variable-region beta-chain (V beta) elements irrespective of the other variable components of the TCR. These have been termed 'superantigens', and here we are concerned with one type of superantigen, the toxins produced by Staphylococcus aureus. T cells have been found that bear closely related members of the same V beta family but respond differently to S. aureus toxins; in particular, cells bearing the human V beta 13.2 element respond to toxin SEC2, whereas cells bearing human V beta 13.1 do not. We have now defined the residues of the V beta element responsible for this difference, and find that they reside in a region thought to lie on the side of the TCR molecule, away from the conventional antigen/MHC-binding site. The evolutionary conservation of this site may be due to its having an important role in some function of the TCR other than the binding of conventional antigen plus MHC. 相似文献
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Active transport of L-dopa in the intestine 总被引:7,自引:0,他引:7
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Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression 总被引:51,自引:0,他引:51
Although proteins fulfil most of the requirements that biology has for structural and functional components such as enzymes and receptors, RNA can also serve in these capacities. For example, RNA has sufficient structural plasticity to form ribozyme and receptor elements that exhibit considerable enzymatic power and binding specificity. Moreover, these activities can be combined to create allosteric ribozymes that are modulated by effector molecules. It has also been proposed that certain messenger RNAs might use allosteric mechanisms to mediate regulatory responses depending on specific metabolites. We report here that mRNAs encoding enzymes involved in thiamine (vitamin B(1)) biosynthesis in Escherichia coli can bind thiamine or its pyrophosphate derivative without the need for protein cofactors. The mRNA-effector complex adopts a distinct structure that sequesters the ribosome-binding site and leads to a reduction in gene expression. This metabolite-sensing regulatory system provides an example of a 'riboswitch' whose evolutionary origin might pre-date the emergence of proteins. 相似文献
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Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways. Cullins are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex. The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins. F-box proteins bind Skp1 through the F-box motif, and substrates by means of carboxy-terminal protein interaction domains. Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide. 相似文献
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The benthic macroinvertebrate fauna of southern Saskatchewan, Canada, has received little attention relative to other regions of western North America. Therefore, little is known of the related aquatic ecosystem health and biogeography of regional aquatic insects. Here we present the results of an aquatic macroinvertebrate survey for the Pipestone Creek watershed in southeastern Saskatchewan. We qualitatively sampled aquatic macroinvertebrates in 5 sites on 4 dates through spring, summer, and fall 2006. Sampling produced 294 taxa of macroinvertebrates including 25 provincial range extensions to the southeast corner of the province. Presence/absence data of taxa grouped the sites into lentic and lotic sites. However, the relative proportions of the taxa varied greatly among sites, with no 2 sites having a community similarity greater than 50%. Functional feeding group analyses separated the sites into collector-dominated and scraper/grazer-dominated sites. However, the taxonomic make-up of the feeding groups varied among sites and also among dates. A modified Hilsenhoff Biotic Index of the site communities indicated that all were influenced by organic pollution. Results of this study suggest that although the watershed is enormously diverse, its biological communities are likely influenced by organic pollution. Further, range expansions of species found here, such as the stonefly Perlesta placida , have implications for invasion pathways and post-glaciation species islands in a prairie landscape. 相似文献