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Two nuclear localization signals present in the basic-helix 1 domains of MyoD promote its active nuclear translocation and can function independently. 总被引:7,自引:0,他引:7
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M Vandromme J C Cavadore A Bonnieu A Froeschlé N Lamb A Fernandez 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(10):4646-4650
MyoD, a member of the family of helix-loop-helix myogenic factors that plays a crucial role in skeletal muscle differentiation, is a nuclear phosphoprotein. Using microinjection of purified MyoD protein into rat fibroblasts, we show that the nuclear import of MyoD is a rapid and active process, being ATP and temperature dependent. Two nuclear localization signals (NLSs), one present in the basic region and the other in the helix 1 domain of MyoD protein, are demonstrated to be functional in promoting the active nuclear transport of MyoD. Synthetic peptides spanning these two NLSs and biochemically coupled to IgGs can promote the nuclear import of microinjected IgG conjugates in muscle and nonmuscle cells. Deletion analysis reveals that each sequence can function independently within the MyoD protein since concomittant deletion of both sequences is required to alter the nuclear import of this myogenic factor. In addition, the complete cytoplasmic retention of a beta-galactosidase-MyoD fusion mutant protein, double deleted at these two NLSs, argues against the existence of another functional NLS motif in MyoD. 相似文献
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Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs 总被引:4,自引:0,他引:4
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Iyer D Chang D Marx J Wei L Olson EN Parmacek MS Balasubramanyam A Schwartz RJ 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(12):4516-4521
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DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer.
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J E Johnson S J Birren T Saito D J Anderson 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(8):3596-3600
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The Drosophila homologue of vertebrate myogenic-determination genes encodes a transiently expressed nuclear protein marking primary myogenic cells. 总被引:11,自引:5,他引:6
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B M Paterson U Walldorf J Eldridge A Dübendorfer M Frasch W J Gehring 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(9):3782-3786
We have isolated a cDNA clone, called Dmyd for Drosophila myogenic-determination gene, that encodes a protein with structural and functional characteristics similar to the members of the vertebrate MyoD family. Dmyd clone encodes a polypeptide of 332 amino acids with 82% identity to MyoD in the 41 amino acids of the putative helix-loop-helix region and 100% identity in the 13 amino acids of the basic domain proposed to contain the essential recognition code for muscle-specific gene activation. Low-stringency hybridizations indicate that Dmyd is not a member of a multigene family similar to MyoD in vertebrates. Dmyd is a nuclear protein in Drosophila, consistent with its role as a nuclear-gene regulatory factor, and is proposed to be a transiently expressed marker for muscle founder cells. We have used an 8-kilobase promoter fragment from the gene, which contains the first 55 amino acids of the Dmyd protein, joined to lacZ, to follow myogenic precursor cells into muscle fibers with antibodies to beta-galactosidase and to Dmyd. Unlike the myogenic factors in vertebrate muscle cells, Dmyd appears to be expressed at a much lower level in differentiated Drosophila muscles, so Dmyd cannot be followed continuously as a muscle marker. This fact is reflected in the loss of Dmyd RNA expression in 12- to 24-hr embryos, a major period of early myogenesis, as well as in the undetectable level of the nuclear antigen in primary cultures of embryonic and adult Drosophila muscle. 相似文献
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Activation of the myogenin promoter during mouse embryogenesis in the absence of positive autoregulation. 总被引:2,自引:0,他引:2
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T C Cheng B S Tseng J P Merlie W H Klein E N Olson 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(2):561-565
Myogenin, a member of the MyoD family of helix-loop-helix proteins, can induce myogenesis in a wide range of cell types. In addition to activating muscle structural genes, members of the MyoD family can autoactivate their own and cross-activate one another's expression in transfected cells. This has led to the hypothesis that autoregulatory loops among these factors provide a mechanism for amplifying and maintaining the muscle-specific gene expression program in vivo. Here, we make use of myogenin-null mice to directly test this hypothesis. To investigate whether the myogenin protein autoregulates the myogenin gene during embryogenesis, we introduced a myogenin-lacZ transgene into mice harboring a null mutation at the myogenin locus. Despite a severe deficiency of skeletal muscle in myogenin-null neonates, the myogenin-lacZ transgene was expressed normally in myogenic cells throughout embryogenesis. These results show that myogenin is not required for regulation of the myogenin gene and argue against the existence of a myogenin autoregulatory loop in the embryo. 相似文献
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In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation
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Dilworth FJ Seaver KJ Fishburn AL Htet SL Tapscott SJ 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(32):11593-11598
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B H Bennetts L Burnett C G dos Remedios 《Journal of molecular and cellular cardiology》1986,18(9):993-996
Human cardiac muscle has been studied to determine whether the ratio of cardiac alpha-actin to skeletal alpha-actin varies between the different chambers of the human heart taken from a single individual. Using mRNA dot-blots, and DNA probes specific for the cardiac and skeletal alpha-actin isotypes, we have found that both cardiac and skeletal alpha-actin mRNAs are present and co-expressed throughout the human heart. The pattern of alpha-actin co-expression in the left and right ventricles and in the interventricular septum is approximately the same, with cardiac alpha-actin being the dominant isotype (approx. 80% of total). However, the left atrium has a different relative composition of the two actins, with an even higher level of cardiac alpha-actin expression (95% of total). 相似文献