Abstract:
:gamma-Secretase-dependent regulated intramembrane proteolysis of amyloid precursor protein (APP) releases the APP intracellular domain (AICD). The question of whether this domain, like the Notch intracellular domain, is involved in nuclear signalling is highly controversial. Although some reports suggest that AICD regulates the expression of KAI1, glycogen synthase kinase-3beta, Neprilysin and APP, we found no consistent effects of gamma-secretase inhibitors or of genetic deficiencies in the gamma-secretase complex or the APP family on the expression levels of these genes in cells and tissues. Finally, we demonstrate that Fe65, an important AICD-binding protein, transactivates a wide variety of different promoters, including the viral simian virus 40 promoter, independent of AICD coexpression. Overall, the four currently proposed target genes are at best indirectly and weakly influenced by APP processing. Therefore, inhibition of APP processing to decrease Abeta generation in Alzheimer's disease will not interfere significantly with the function of these genes.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Hébert SS,Serneels L,Tolia A,Craessaerts K,Derks C,Filippov MA,Müller U,De Strooper Bdoi
10.1038/sj.embor.7400704subject
Has Abstractpub_date
2006-07-01 00:00:00pages
739-45issue
7eissn
1469-221Xissn
1469-3178pii
7400704journal_volume
7pub_type
杂志文章相关文献
EMBO REPORTS文献大全abstract::Immune signaling networks must be tunable to alleviate fitness costs associated with immunity and, at the same time, robust against pathogen interferences. How these properties mechanistically emerge in plant immune signaling networks is poorly understood. Here, we discovered a molecular mechanism by which the model p...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201643051
更新日期:2017-03-01 00:00:00
abstract::Research into the extreme feats of endurance that humans and some animals achieve has uncovered a range of metabolic and physiological adaptations along with their evolutionary origins. ...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.15252/embr.201949396
更新日期:2019-11-05 00:00:00
abstract::Defects in protein folding and the proteasomal pathway have been linked with many neurodegenerative diseases. PLIC-1 (protein linking IAP to the cytoskeleton) is a ubiquitin-like protein that binds to the ubiquitin-interacting motif (UIM) of the proteasomal subunit S5a. Here, we show that PLIC-1 also binds to the UIM ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400823
更新日期:2006-12-01 00:00:00
abstract::Plasma membrane PI4P is an important direct regulator of many processes that occur at the plasma membrane and also a biosynthetic precursor of PI(4,5)P2 and its downstream metabolites. The majority of this PI4P pool is synthesized by an evolutionarily conserved complex, which has as its core the PI 4-kinase PI4KIIIα (...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201439151
更新日期:2015-03-01 00:00:00
abstract::Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood. Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explai...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201541542
更新日期:2016-02-01 00:00:00
abstract::The natural progressive dysfunction of most living organisms-ageing-has captured the attention of several studies, with the intention to develop rejuvenation strategies. Evidence is emerging of a positive correlation between natural ageing and chromosomal instability (CIN). In this issue of EMBO Reports, Barroso-Vilar...
journal_title:EMBO reports
pub_type: 评论,新闻
doi:10.15252/embr.202050322
更新日期:2020-05-06 00:00:00
abstract::STK38 (also known as NDR1) is a Hippo pathway serine/threonine protein kinase with multifarious functions in normal and cancer cells. Using a context-dependent proximity-labeling assay, we identify more than 250 partners of STK38 and find that STK38 modulates its partnership depending on the cellular context by increa...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948150
更新日期:2019-11-05 00:00:00
abstract::Estrogen receptors (ERs) orchestrate both transcriptional and non-genomic functions in response to estrogens, xenoestrogens and signals emanating from growth factor signalling pathways. The pleiotropic and tissue-specific effects of estrogens are likely to be mediated by the differential expression of distinct estroge...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1093/embo-reports/kve185
更新日期:2001-09-01 00:00:00
abstract::The systematic recording and management of experimental data in academic life science research remains an open problem. EPFL engaged in a program of ELN/LIMS deployment 6 years ago, encountering a host of fundamental questions at the institutional level and in each single laboratory. Here, based on our experience we a...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201949862
更新日期:2020-03-04 00:00:00
abstract::Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin-like protein fr...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201540851
更新日期:2016-02-01 00:00:00
abstract::The actin cytoskeleton operates in a multitude of cellular processes including cell shape and migration, mechanoregulation, and membrane or organelle dynamics. However, its filamentous properties and functions inside the mammalian cell nucleus are less well explored. We previously described transient actin assembly at...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202050758
更新日期:2020-11-05 00:00:00
abstract::The angiotensin II type 1 (AT(1)) receptor is a G protein-coupled receptor that has a crucial role in the development of load-induced cardiac hypertrophy. Here, we show that cell stretch leads to activation of the AT(1) receptor, which undergoes an anticlockwise rotation and a shift of transmembrane (TM) 7 into the li...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7401157
更新日期:2008-02-01 00:00:00
abstract::Global climate change and the increasing human population require crop varieties with higher yield and draught resistance. But meeting both goals is not an easy task for breeders and plant science. ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202051598
更新日期:2020-11-29 00:00:00
abstract::The modification of proteins by the small ubiquitin-like modifier (SUMO) is known to regulate an increasing array of cellular processes. SUMOylation of the mitochondrial fission GTPase dynamin-related protein 1 (DRP1) stimulates mitochondrial fission, suggesting that SUMOylation has an important function in mitochondr...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2009.86
更新日期:2009-07-01 00:00:00
abstract::Accumulating evidence highlights the role of histone acetyltransferase GCN5 in the regulation of cell metabolism in metazoans. Here, we report that GCN5 is a negative regulator of autophagy, a lysosome-dependent catabolic mechanism. In animal cells and Drosophila, GCN5 inhibits the biogenesis of autophagosomes and lys...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948335
更新日期:2020-01-07 00:00:00
abstract::The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1) maintains the silent state by inhibiting the transcription machinery and chromatin remodelling at core promoters. Using immunoprecipitation of in vivo formald...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400260
更新日期:2004-10-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, whose best-understood mechanism is sprouting. However, therapeutic VEGF delivery to ischemic muscle induces angiogenesis by the alternative process of intussusception, or vascular splitting, whose molecular regulation is essentially unk...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201745054
更新日期:2018-05-01 00:00:00
abstract::Recruitment of beta-arrestin (beta-arr) to agonist-stimulated G-protein-coupled receptors (GPCRs) has a crucial role in controlling signalling efficacy and selectivity. When translocated to the receptor, beta-arr is believed to undergo important conformational rearrangement necessary for its downstream actions. To pro...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400373
更新日期:2005-04-01 00:00:00
abstract::The human XAB1/MBDin GTPase and its close homologues form one of the ten phylogenetically distinct families of the SIMIBI (after signal recognition particle, MinD and BioD) class of phosphate-binding loop NTPases. The genomic context and the partners identified for the archaeal and eukaryotic homologues indicate that ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400958
更新日期:2007-06-01 00:00:00
abstract::Brinker is a nuclear protein that antagonizes Dpp signalling in Drosophila. Its expression is negatively regulated by Dpp. Here, we show that Brinker represses Ultrabithorax (Ubx) in the embryonic midgut, a HOX gene that activates, and responds to, the localized expression of Dpp during endoderm induction. We find tha...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kve068
更新日期:2001-04-01 00:00:00
abstract::There is a great interest in determining the impact of p53 on ageing and, for this, it is important to discriminate among the known causes of ageing. Telomere loss is a well-established source of age-associated damage, which by itself can recapitulate ageing in mouse models. Here, we have used a genetic approach to in...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400667
更新日期:2006-05-01 00:00:00
abstract::Like many transcription regulators, histone methyltransferases G9a and G9a-like protein (GLP) can act gene-specifically as coregulators, but mechanisms controlling this specificity are mostly unknown. We show that adjacent post-translational methylation and phosphorylation regulate binding of G9a and GLP to heterochro...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201744060
更新日期:2017-08-01 00:00:00
abstract::The crucial role of ubiquitin signalling in genome-integrity maintenance was first recognized in 1987 by Stefan Jentsch and Alex Varshavsky, who showed that Rad6-the repair protein involved in DNA damage tolerance-is a ubiquitin-conjugating enzyme. Although this discovery inspired extensive research and led to the dis...
journal_title:EMBO reports
pub_type:
doi:10.1038/embor.2010.180
更新日期:2010-12-01 00:00:00
abstract::The receptor-evoked Ca(2+) signal is sensed and translated by mitochondria. Physiological cytoplasmic Ca(2+) ([Ca(2+)]c) oscillations result in mitochondrial Ca(2+) ([Ca(2+)]m) oscillations, while large and sustained [Ca(2+)]c increase results in a pathologic increase in basal [Ca(2+)]m and in Ca(2+) accumulation. The...
journal_title:EMBO reports
pub_type: 评论,杂志文章
doi:10.1002/embr.201438446
更新日期:2014-03-01 00:00:00
abstract::PTIP regulates gene transcription by controlling the methylation of histone H3, and also has important roles in cellular responses to DNA damage or to perturbed DNA replication. The available data suggest that the functions of PTIP in transcription and preserving genome stability might be independent and mediated by f...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/embor.2009.21
更新日期:2009-03-01 00:00:00
abstract::HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-κB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between t...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2012.24
更新日期:2012-05-01 00:00:00
abstract::Despite its limited resources, Portugal has gained a prominent position in research on malaria. Several historical and personal factors have contributed to this achievement. ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202051692
更新日期:2021-01-10 00:00:00
abstract::Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regul...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201541143
更新日期:2016-03-01 00:00:00
abstract::Although iron is required for cell proliferation, iron-dependent programmed cell death serves as a critical barrier to tumor growth and metastasis. Emerging evidence suggests that iron-mediated lipid oxidation also facilitates immune eradication of cancer. However, the regulatory mechanisms of iron metabolism in cance...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202051162
更新日期:2021-01-04 00:00:00
abstract::The Vav family of proteins are guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases, which regulate various cellular functions, including T-cell activation. They contain a catalytic Dbl homology (DH) domain that is invariably followed by a pleckstrin homology (PH) domain, which is often required fo...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2008.80
更新日期:2008-07-01 00:00:00