Abstract:
:The leukemic fusion gene AML1-MDS1-EVI1 (AME) encodes a chimeric transcription factor that results from the t(3,21)(q26;q22) translocation seen in patients with acute myeloid leukemia, with therapy-related myelodysplastic syndrome, or with chronic myeloid leukemia in blast crisis. The myeloid transcription factor CEBPA is crucial for normal granulopoiesis. Here, we found that conditional expression of AME suppresses CEBPA protein by 90.8% and DNA-binding activity by 93.9%. In contrast, CEBPA mRNA levels remained unchanged. In addition, we detected no differences in CEBPA mRNA levels in leukemic blasts of patients carrying the AME translocation (n = 8) compared to acute myeloid leukemia patients with a normal karyotype (n = 9). CEBPA protein and binding activity, however, were reduced significantly (100% and 92.1%, respectively) in AME patient samples. Furthermore, we observed that calreticulin (CRT), a putative inhibitor of CEBPA translation, was strongly activated after induction of AME in the cell-line system (14.8-fold) and in AME patient samples (12.2-fold). Moreover, inhibition of CRT by small interfering RNA powerfully restored CEBPA levels. These results identify CEBPA as a key target of the leukemic fusion protein AME and suggest that modulation of CEBPA by CRT may represent a mechanism involved in the differentiation block in AME leukemias.
journal_name
Proc Natl Acad Sci U S Aauthors
Helbling D,Mueller BU,Timchenko NA,Hagemeijer A,Jotterand M,Meyer-Monard S,Lister A,Rowley JD,Huegli B,Fey MF,Pabst Tdoi
10.1073/pnas.0404731101keywords:
subject
Has Abstractpub_date
2004-09-07 00:00:00pages
13312-7issue
36eissn
0027-8424issn
1091-6490pii
0404731101journal_volume
101pub_type
杂志文章abstract::The presence of nerve growth factor (NGF) mRNA and protein in the rat central nervous system is documented. Blot-hybridization analysis showed an abundance of NGF mRNA in the hippocampus, cerebral cortex, and olfactory bulb. Enzyme immunoassay confirmed significant levels of a NGF-like protein in the hippocampus and c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.3.817
更新日期:1986-02-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinase kinase is an enzyme that activates the growth factor-regulated MAP kinase in vitro by a mechanism that involves direct phosphorylation of MAP kinase on tyrosine and threonine residues. MAP kinase kinase is stimulated by growth factor treatment of cells and has been shown to be in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.11.5143
更新日期:1993-06-01 00:00:00
abstract::A careful review of the literature in political science and neighboring social science disciplines shows that prevailing assumptions in the international development policy community about improved governance as a principal mechanism to reduce poverty in Africa rests more on faith than science. Conventional policy mod...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0700696104
更新日期:2007-10-23 00:00:00
abstract::The N,N'-diacetyllactosediamine (lacdiNAc) pathway of complex-type oligosaccharide synthesis is controlled by a UDP-GalNAc:GlcNAc beta-R beta 1-->4-N-acetylgalac-tesaminyltransferase (beta 4-GalNAcT) that acts analogously to the common UDP-Gal:GlcNAc beta-R beta 1-->4-galactosyltransferase (beta 4-GalT). LacdiNAc-base...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.19.10111
更新日期:1996-09-17 00:00:00
abstract::A decade ago it was discovered that mature birds are able to regenerate hair cells, the receptors for auditory perception. This surprising finding generated hope in the field of auditory neuroscience that new hair cells someday may be coaxed to form in another class of warm-blooded vertebrates, mammals. We have made c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.22.11714
更新日期:2000-10-24 00:00:00
abstract::Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1709203114
更新日期:2017-08-08 00:00:00
abstract::Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell-deficient (TCRδ-KO) mice and control wild-type mice with Plasmodium bergh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1204480109
更新日期:2012-07-24 00:00:00
abstract::The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of alpha(2)GABA type A (GABA(A)) receptors to the effects of benzodiazepines on sleep and waking oscillatory pat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0306975101
更新日期:2004-03-09 00:00:00
abstract::When purified dimers of hemagglutinin-neuraminidase molecules released by protease digestion from three strains of human parainfluenza virus 1 were used in crystallization trials, long thin needle crystals formed. Electron microscopic analysis of these needle crystals revealed that they are composed of stacks of tripl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.4.1523
更新日期:1993-02-15 00:00:00
abstract::From our current understanding of the genetic basis of development and pattern formation in Drosophila and vertebrates it is commonly thought that clusters of Hox genes sculpt the morphology of animals in specific body regions. Based on Hox gene conservation throughout the animal kingdom it is proposed that these gene...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.6.3030
更新日期:1998-03-17 00:00:00
abstract::Ouabain-sensitive uncoupled Na+ efflux has been studied in human, pig, and rat red cells and in vesicles containing reconstituted kidney Na+/K+ pumps obtained from these same species. The red cells from the different species gave qualitatively similar results; the uncoupled Na+ efflux was 15-30% of the Na+/K+ exchange...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.21.9881
更新日期:1994-10-11 00:00:00
abstract::Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1301190110
更新日期:2013-05-21 00:00:00
abstract::Variation in the multiplication rate of blood stage malaria parasites is often positively correlated with the severity of the disease they cause. The rodent malaria parasite Plasmodium yoelii yoelii has strains with marked differences in multiplication rate and pathogenicity in the blood. We have used genetic analysis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811430106
更新日期:2009-04-28 00:00:00
abstract::Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1121557109
更新日期:2012-02-28 00:00:00
abstract::The midcycle luteinizing hormone (LH) surge triggers several tightly linked ovarian processes, including steroidogenesis, oocyte maturation, and ovulation. We designed studies to determine whether epidermal growth factor receptor (EGFR)-mediated signaling might serve as a common regulator of these activities. Our resu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0508521102
更新日期:2005-11-08 00:00:00
abstract::Human genetic studies have given evidence of familial, disease-causing mutations in the analogous amino acid residue shared by three related RNA binding proteins causative of three neurological diseases. Alteration of aspartic acid residue 290 of hnRNPA2 to valine is believed to predispose patients to multisystem prot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1806174115
更新日期:2018-10-16 00:00:00
abstract::The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1312296111
更新日期:2014-02-18 00:00:00
abstract::Because many survivors of mass extinctions do not participate in postrecovery diversifications, and therefore fall into a pattern that can be termed "Dead Clade Walking" (DCW), the effects of mass extinctions extend beyond the losses observed during the event itself. Analyses at two taxonomic levels provide a first-or...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.102163299
更新日期:2002-06-11 00:00:00
abstract::Human chromosome 22q11.2 has been implicated in various behavioral abnormalities, including schizophrenia and other neuropsychiatric/behavioral disorders. However, the specific genes within 22q11.2 that contribute to these disorders are still poorly understood. Here, we show that an approximately 200-kb segment of hum...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0509635102
更新日期:2005-12-27 00:00:00
abstract::Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. Here, we introduce an approach based on diffuse...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1215473110
更新日期:2013-01-08 00:00:00
abstract::The 3' flanking region of the apolipoprotein B (apoB) gene contains a hypervariable region consisting of a variable number of tandemly repeated short A + T-rich DNA sequences (VNTRs). We present a general method that utilizes the polymerase chain reaction to rapidly and accurately type this and other VNTR loci. We use...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.1.212
更新日期:1989-01-01 00:00:00
abstract::Alternative adaptations-different adaptive phenotypes maintained in the same life stage and the same population but not necessarily simultaneously expressed in the same individual-represent contrasting character sets produced by the same genome, in effect allowing a single species to occupy more than one sympatric nic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.5.1388
更新日期:1986-03-01 00:00:00
abstract::A recombinant plasmid containing sequences complementary to human pro-alpha l(I) collagen mRNA was used for the chromosomal assignment of the pro-alpha l(I) collagen gene. Restriction endonuclease analysis of DNA from mouse-human and Chinese hamster-human somatic cell hybrids revealed cosegregation with human chromoso...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.21.6627
更新日期:1982-11-01 00:00:00
abstract::We have recently shown that p-terphenyl-3,5,3',5'-tetracarboxylic acid adsorbed on graphite self-assembles into a two-dimensional rhombus random tiling. This tiling is close to ideal, displaying long-range correlations punctuated by sparse localized tiling defects. In this article we explore the analogy between dynami...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0902443106
更新日期:2009-09-08 00:00:00
abstract::Many cyanobacteria alter their phycobilisome composition in response to changes in light wavelength in a process termed complementary chromatic adaptation. Mutant strains FdR1 and FdR2 of the filamentous cyanobacterium Fremyella diplosiphon are characterized by aberrant chromatic adaptation. Instead of adjusting to di...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.20.9415
更新日期:1992-10-15 00:00:00
abstract::Natural transformation (i.e., the uptake of DNA and its stable integration in the chromosome) is a major mechanism of horizontal gene transfer in bacteria. Although the vast majority of bacterial genomes carry the genes involved in natural transformation, close relatives of naturally transformable species often appear...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1909374116
更新日期:2019-09-10 00:00:00
abstract::Murine and human cDNAs, related to but distinct from c-raf-1, have been isolated and designated mA-raf and hA-raf, respectively. The mA-raf and hA-raf cDNAs detect the same murine and human fragments in Southern blots of restriction enzyme-cleaved murine and human cellular DNA. The murine restriction enzyme fragments ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.11.3934
更新日期:1986-06-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) glutamate receptor-mediated increases in intracellular calcium are thought to play a critical role in synaptic plasticity. The mechanisms by which changes in cytoplasmic calcium transmit the glutamate signal to the nucleus, which is ultimately important for long-lasting neuronal responses, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.10.5773
更新日期:1998-05-12 00:00:00
abstract::The causes of major and rapid transitions observed in biological macroevolution as well as in the evolution of social systems are a subject of much debate. Here we identify the proximate causes of crashes and recoveries that arise dynamically in a model system in which populations of (molecular) species coevolve with ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.032618499
更新日期:2002-02-19 00:00:00
abstract::The harvest of wildlife for human consumption is valued at several billion dollars annually and provides an essential source of meat for hundreds of millions of rural people living in poverty. This harvest is also considered among the greatest threats to biodiversity throughout Africa, Asia, and Latin America. Economi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1011526108
更新日期:2011-08-23 00:00:00