共查询到20条相似文献,搜索用时 15 毫秒
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Jayapal SR Lee KL Ji P Kaldis P Lim B Lodish HF 《The Journal of biological chemistry》2010,285(51):40252-40265
Terminal differentiation of mammalian erythroid progenitors involves 4-5 cell divisions and induction of many erythroid important genes followed by chromatin and nuclear condensation and enucleation. The protein levels of c-Myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G(1) phase and enucleation, suggesting possible roles for c-Myc in either or both of these processes. Here we demonstrate that ectopic Myc expression affects terminal erythroid maturation in a dose-dependent manner. Expression of Myc at physiological levels did not affect erythroid differentiation or cell cycle shutdown but specifically blocked erythroid nuclear condensation and enucleation. Continued Myc expression prevented deacetylation of several lysine residues in histones H3 and H4 that are normally deacetylated during erythroid maturation. The histone acetyltransferase Gcn5 was up-regulated by Myc, and ectopic Gcn5 expression partially blocked enucleation and inhibited the late stage erythroid nuclear condensation and histone deacetylation. When overexpressed at levels higher than the physiological range, Myc blocked erythroid differentiation, and the cells continued to proliferate in cytokine-free, serum-containing culture medium with an early erythroblast morphology. Gene expression analysis demonstrated the dysregulation of erythropoietin signaling pathway and the up-regulation of several positive regulators of G(1)-S cell cycle checkpoint by supraphysiological levels of Myc. These results reveal an important dose-dependent function of Myc in regulating terminal maturation in mammalian erythroid cells. 相似文献
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Hiratsu K Mitsuda N Matsui K Ohme-Takagi M 《Biochemical and biophysical research communications》2004,321(1):172-178
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The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation 总被引:8,自引:0,他引:8
Adhikary S Marinoni F Hock A Hulleman E Popov N Beier R Bernard S Quarto M Capra M Goettig S Kogel U Scheffner M Helin K Eilers M 《Cell》2005,123(3):409-421
The Myc oncoprotein forms a binary activating complex with its partner protein, Max, and a ternary repressive complex that, in addition to Max, contains the zinc finger protein Miz1. Here we show that the E3 ubiquitin ligase HectH9 ubiquitinates Myc in vivo and in vitro, forming a lysine 63-linked polyubiquitin chain. Miz1 inhibits this ubiquitination. HectH9-mediated ubiquitination of Myc is required for transactivation of multiple target genes, recruitment of the coactivator p300, and induction of cell proliferation by Myc. HectH9 is overexpressed in multiple human tumors and is essential for proliferation of a subset of tumor cells. Our results suggest that site-specific ubiquitination regulates the switch between an activating and a repressive state of the Myc protein, and they suggest a strategy to interfere with Myc function in vivo. 相似文献
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The novel cancer/testis antigen gene, NY-SAR-35, is expressed exclusively in normal testis and in various histological types
of tumor. However, the NY-SAR-35 gene expression is observed to be aberrant in several cancer cell lines and tissues. The
analysis of methylation status of the NY-SAR-35 gene promoter in various cancer cell lines showed that its expression was
related to methylation of the promoter region. Treatment of human cancer cell lines with the demethylating agent 5-aza-2′-deoxycytidine
activated the expression of the NY-SAR-35 gene. In addition, transfection experiments on various fragments of the CpG-rich
gene promoter indicate that in vitro methylation of the NY-SAR-35 gene promoter results in the loss of promoter activity.
The expression of NY-SAR-35 is therefore activated by hypomethylation of the CpG island in the gene promoter. 相似文献
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Deletion by in vivo recombination shows that the 28-kilodalton cytolytic polypeptide from Bacillus thuringiensis subsp. israelensis is not essential for mosquitocidal activity. 总被引:4,自引:1,他引:4 下载免费PDF全文
The cytA gene encoding the 28-kDa polypeptide of Bacillus thuringiensis subsp. israelensis crystals was disrupted in the 72-MDa resident plasmid by in vivo recombination, thus indicating that homologous recombination occurs in B. thuringiensis. The absence of the 28-kDa protein in B. thuringiensis did not affect the crystallization of the other toxic components of the parasporal body (68-, 125-, and 135-kDa polypeptides). The absence of the 28-kDa protein abolished the hemolytic activity of B. thuringiensis subsp. israelensis crystals. However, the mosquitocidal activity of the 28-kDa protein-free crystals did not differ significantly from that of the wild-type crystals when tested on Aedes aegypti and Culex pipiens larvae. The 28-kDa protein contributed slightly to the toxicity to Anopheles stephensi larvae. This indicates that the 28-kDa protein is not essential for mosquitocidal activity, at least against the three species tested. 相似文献
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Toledano-Katchalski H Nir R Volohonsky G Volk T 《Development (Cambridge, England)》2007,134(19):3473-3481
The even spreading of mesoderm cells in the Drosophila embryo is essential for its proper patterning by ectodermally derived signals. In how germline clone embryos, defects in mesoderm spreading lead to a partial loss of dorsal mesoderm derivatives. HOW is an RNA-binding protein that is thought to regulate diverse mRNA targets. To identify direct HOW targets, we implemented a series of selection methods on mRNAs whose levels were elevated in how germline clone embryos during the stage of mesoderm spreading. Four mRNAs were found to be specifically elevated in the mesoderm of how germline clone embryos, and to exhibit specific binding to HOW via their 3' UTRs. Importantly, overexpression of three of these genes phenocopied the mesoderm-spreading phenotype of how germline clone embryos. Further analysis showed that overexpressing one of these genes, miple (a Drosophila midkine and pleiotrophin heparin-binding growth factor), in the mesoderm led to abnormal scattered MAPK activation, a phenotype that might explain the abnormal mesoderm spreading. In addition, the number of EVE-positive cells, which are responsive to receptor tyrosine kinase (RTK) signaling, was increased following Miple overexpression in the mesoderm and appeared to be dependent on Heartless function. In summary, our analysis suggests that HOW downregulates the levels of a number of mRNA species in the mesoderm in order to enable proper mesoderm spreading during early embryogenesis. 相似文献
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CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells 下载免费PDF全文
Opavsky R Wang SH Trikha P Raval A Huang Y Wu YZ Rodriguez B Keller B Liyanarachchi S Wei G Davuluri RV Weinstein M Felsher D Ostrowski M Leone G Plass C 《PLoS genetics》2007,3(9):1757-1769
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Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta 总被引:13,自引:0,他引:13
Itoh M Kim CH Palardy G Oda T Jiang YJ Maust D Yeo SY Lorick K Wright GJ Ariza-McNaughton L Weissman AM Lewis J Chandrasekharappa SC Chitnis AB 《Developmental cell》2003,4(1):67-82
Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells. 相似文献
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A retrovirus-like zinc domain is essential for translational repression of bacteriophage T4 gene 32 总被引:5,自引:0,他引:5
Y Shamoo K R Webster K R Williams W H Konigsberg 《The Journal of biological chemistry》1991,266(13):7967-7970
Gene 32 protein (gp32), a single-stranded DNA-binding protein from bacteriophage T4, contains a zinc-binding subdomain with sequence homologies to the 3-cysteine/1-histidine zinc-binding motif found in a variety of retroviruses and plant viruses. In vitro studies suggest that autoregulation of gp32 occurs at the level of translation by gp32 specifically binding gene 32 mRNA at an unusual stem-loop structure that can be modeled as an RNA pseudoknot. Nucleation of gp32 binding via this pseudoknot is thought to be needed to facilitate cooperative binding of gp32 through a largely unstructured region that overlaps the ribosome binding site (McPheeters, D. S., Stormo, G. D., and Gold, L. (1988) J. Mol. Biol. 201, 517-535). Removal of Zn(II) from gp32 results in a protein that retains the ability to bind single-stranded RNA with high affinity but is unable to specifically autoregulate itself at the level of translation. Deletion of the pseudoknot sequences from the gene 32 autoregulatory region results in an mRNA that cannot be repressed by gp32. These results suggest that the zinc-binding subdomain of gp32 plays an essential role in autoregulation by providing a critical element necessary for nucleating cooperative binding at the gene 32 mRNA pseudoknot. 相似文献
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MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline 总被引:11,自引:0,他引:11
Carmell MA Girard A van de Kant HJ Bourc'his D Bestor TH de Rooij DG Hannon GJ 《Developmental cell》2007,12(4):503-514
Small RNAs associate with Argonaute proteins and serve as sequence-specific guides for regulation of mRNA stability, productive translation, chromatin organization, and genome structure. In animals, the Argonaute superfamily segregates into two clades. The Argonaute clade acts in RNAi and in microRNA-mediated gene regulation in partnership with 21-22 nt RNAs. The Piwi clade, and their 26-30 nt piRNA partners, have yet to be assigned definitive functions. In mice, two Piwi-family members have been demonstrated to have essential roles in spermatogenesis. Here, we examine the effects of disrupting the gene encoding the third family member, MIWI2. Miwi2-deficient mice display a meiotic-progression defect in early prophase of meiosis I and a marked and progressive loss of germ cells with age. These phenotypes may be linked to an inappropriate activation of transposable elements detected in Miwi2 mutants. Our observations suggest a conserved function for Piwi-clade proteins in the control of transposons in the germline. 相似文献
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Quigley JG Yang Z Worthington MT Phillips JD Sabo KM Sabath DE Berg CL Sassa S Wood BL Abkowitz JL 《Cell》2004,118(6):757-766
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Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus 总被引:143,自引:0,他引:143
All cells transformed by Rous sarcoma virus contain levels of phosphotyrosine in protein which are 6–10 fold greater than the very low levels present in uninfected cells. The increase is due largely to modification of cellular polypeptides. The abundance of phosphorylated tyrosines in protein in cells infected with tsLA29, a mutant of Rous sarcoma virus which is temperature-sensitive for cellular transformation, increases to 60% of maximum within 60 min of a shift to the permissive temperature and drops to a level close to that in uninfected cells within 60 min of a shift to the restrictive temperature. In light of the fact that pp60src phosphorylates tyrosine in vitro, these results suggest strongly that the modification of one or more cellular polypeptides by way of pp60src is critical for cellular transformation by Rous sarcoma virus. There is, however, no increase in the abundance of phosphotyrosine in protein in mouse cells transformed by Kirsten sarcoma virus, Moloney sarcoma virus, or SV40 virus, in chick embryo cells infected with avian myelocytomatosis virus MC29, and in rat and hamster cells transformed by polyoma virus. Thus increased phosphorylation of tyrosine is neither a universal mechanism of transformation nor an inevitable secondary cellular response to transformation. 相似文献
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A Dictyostelium morphogen that is essential for stalk cell formation is generated by a subpopulation of prestalk cells 总被引:2,自引:0,他引:2
The stalk cell differentiation inducing factor (DIF) has the properties required of a morphogen responsible for pattern regulation during the pseudoplasmodial stage of Dictyostelium development. It induces prestalk cell formation and inhibits prespore cell formation, but there is as yet no strong evidence for a morphogenetic gradient of DIF. We have measured DIF accumulation by monolayers of isolated prestalk and prespore cells in an attempt to provide evidence for such a gradient. DIF is accumulated in the largest quantities by a subpopulation of prestalk cells that specifically express the DIF-inducible genes pDd56 and pDd26. Since it has been shown recently that cells that express pDd56 are localized in the central core of the prestalk cell region of the pseudoplasmodia, our current results suggest a morphogenetic gradient generated by this region. 相似文献