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M. B. Castillo M. D. Gonzalez G. Burton C. P. Lantos A. Roldán 《Cellular and molecular life sciences : CMLS》1983,39(6):617-618
Summary A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11-ol-3, 20-dione and pregna-1,4-diene-11-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.Acknowledgments. This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina to the Instituto de Biologia y Medicina Experimental and the Programa de Regulación Hormonal y Metabólica as well as by financial help from the Secretaría de Ciencia y Tecnología. 相似文献
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So Young Lee Juanma Ramirez Maribel Franco Benoît Lectez Monika Gonzalez Rosa Barrio Ugo Mayor 《Cellular and molecular life sciences : CMLS》2014,71(14):2747-2758
Ubiquitination, the covalent attachment of ubiquitin to a target protein, regulates most cellular processes and is involved in several neurological disorders. In particular, Angelman syndrome and one of the most common genomic forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during brain development. We have now devised a protocol to screen for substrates of this particular ubiquitin ligase. In a neuronal cell system, we find direct ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is targeted for degradation upon ubiquitination by Ube3a, indicating that degradation might not be the only effect of Ube3a on its substrates. Furthermore, we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of ubiquitinated proteins, further supporting the biochemical evidence of interaction obtained in neuronal cells. 相似文献
6.
van Kasteren SI Kramer HB Jensen HH Campbell SJ Kirkpatrick J Oldham NJ Anthony DC Davis BG 《Nature》2007,446(7139):1105-1109
One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, we have found many fewer genes than we would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein production methods typically produce PTM mixtures within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here we report a chemical tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, we created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chemistry provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. We therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system. 相似文献
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PTC124 targets genetic disorders caused by nonsense mutations 总被引:1,自引:0,他引:1
Welch EM Barton ER Zhuo J Tomizawa Y Friesen WJ Trifillis P Paushkin S Patel M Trotta CR Hwang S Wilde RG Karp G Takasugi J Chen G Jones S Ren H Moon YC Corson D Turpoff AA Campbell JA Conn MM Khan A Almstead NG Hedrick J Mollin A Risher N Weetall M Yeh S Branstrom AA Colacino JM Babiak J Ju WD Hirawat S Northcutt VJ Miller LL Spatrick P He F Kawana M Feng H Jacobson A Peltz SW Sweeney HL 《Nature》2007,447(7140):87-91
Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options. 相似文献
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Lissauer JJ Fabrycky DC Ford EB Borucki WJ Fressin F Marcy GW Orosz JA Rowe JF Torres G Welsh WF Batalha NM Bryson ST Buchhave LA Caldwell DA Carter JA Charbonneau D Christiansen JL Cochran WD Desert JM Dunham EW Fanelli MN Fortney JJ Gautier TN Geary JC Gilliland RL Haas MR Hall JR Holman MJ Koch DG Latham DW Lopez E McCauliff S Miller N Morehead RC Quintana EV Ragozzine D Sasselov D Short DR Steffen JH 《Nature》2011,470(7332):53-58
When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation. 相似文献
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Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by genome and transcriptome analyses 总被引:8,自引:0,他引:8
RJ O'Connell MR Thon S Hacquard SG Amyotte J Kleemann MF Torres U Damm EA Buiate L Epstein N Alkan J Altmüller L Alvarado-Balderrama CA Bauser C Becker BW Birren Z Chen J Choi JA Crouch JP Duvick MA Farman P Gan D Heiman B Henrissat RJ Howard M Kabbage C Koch B Kracher Y Kubo AD Law MH Lebrun YH Lee I Miyara N Moore U Neumann K Nordström DG Panaccione R Panstruga M Place RH Proctor D Prusky G Rech R Reinhardt JA Rollins S Rounsley CL Schardl DC Schwartz N Shenoy K Shirasu UR Sikhakolli K Stüber 《Nature genetics》2012,44(9):1060-1065
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Hüffmeier U Uebe S Ekici AB Bowes J Giardina E Korendowych E Juneblad K Apel M McManus R Ho P Bruce IN Ryan AW Behrens F Lascorz J Böhm B Traupe H Lohmann J Gieger C Wichmann HE Herold C Steffens M Klareskog L Wienker TF Fitzgerald O Alenius GM McHugh NJ Novelli G Burkhardt H Barton A Reis A 《Nature genetics》2010,42(11):996-999
Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. 相似文献