Abstract：
:Nuclear exclusion of the PTEN (phosphatase and tensin homologue deleted in chromosome 10) tumour suppressor has been associated with cancer progression. However, the mechanisms leading to this aberrant PTEN localization in human cancers are currently unknown. We have previously reported that ubiquitinylation of PTEN at specific lysine residues regulates its nuclear-cytoplasmic partitioning. Here we show that functional promyelocytic leukaemia protein (PML) nuclear bodies co-ordinate PTEN localization by opposing the action of a previously unknown PTEN-deubiquitinylating enzyme, herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), and that the integrity of this molecular framework is required for PTEN to be able to enter the nucleus. We find that PTEN is aberrantly localized in acute promyelocytic leukaemia, in which PML function is disrupted by the PML-RARalpha fusion oncoprotein. Remarkably, treatment with drugs that trigger PML-RARalpha degradation, such as all-trans retinoic acid or arsenic trioxide, restore nuclear PTEN. We demonstrate that PML opposes the activity of HAUSP towards PTEN through a mechanism involving the adaptor protein DAXX (death domain-associated protein). In support of this paradigm, we show that HAUSP is overexpressed in human prostate cancer and is associated with PTEN nuclear exclusion. Thus, our results delineate a previously unknown PML-DAXX-HAUSP molecular network controlling PTEN deubiquitinylation and trafficking, which is perturbed by oncogenic cues in human cancer, in turn defining a new deubiquitinylation-dependent model for PTEN subcellular compartmentalization.
journal_name
Naturejournal_title
Natureauthors
Song MS,Salmena L,Carracedo A,Egia A,Lo-Coco F,Teruya-Feldstein J,Pandolfi PPdoi
10.1038/nature07290subject
Has Abstractpub_date
2008-10-09 00:00:00pages
813-7issue
7214eissn
0028-0836issn
1476-4687pii
nature07290journal_volume
455pub_type
杂志文章相关文献
NATURE文献大全abstract：:The versatility of Ca2+ signals derives from their spatio-temporal organization. For Ca2+ signals initiated by inositol-1,4,5-trisphosphate (InsP3), this requires local interactions between InsP3 receptors (InsP3Rs) mediated by their rapid stimulation and slower inhibition\ by cytosolic Ca2+. This allows hierarchical ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07763
更新日期：2009-04-02 00:00:00
abstract：:A popular metaphor for the representation of numbers in the brain is the 'mental number line', in which numbers are represented in a continuous, quantity-based analogical format. Here we show that patients with hemispatial neglect misplace the midpoint of a numerical interval when asked to bisect it (for example, stat...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/417138a
更新日期：2002-05-09 00:00:00
abstract：:Determining the chronology for the assembly of planetary bodies in the early Solar System is essential for a complete understanding of star- and planet-formation processes. Various radionuclide chronometers (applied to meteorites) have been used to determine that basaltic lava flows on the surface of the asteroid Vest...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature00995
更新日期：2002-08-29 00:00:00
abstract：:The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and m...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13721
更新日期：2014-09-11 00:00:00
abstract：:Transcriptional activator proteins (activators) function, at least in part, by increasing preinitiation complex assembly (for reviews see refs 1-4). Previous studies have shown that an acidic activator forms a contact with the general transcription factor TFIIB (refs 5-7) and recruits it into the preinitiation complex...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/371717a0
更新日期：1994-10-20 00:00:00
abstract：:Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+]i) to at least 100 microM near the sites of vesicle f...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35022702
更新日期：2000-08-24 00:00:00
abstract：:Although cell migration is crucial for neural development, molecular mechanisms guiding neuronal migration have remained unclear. Here we report that the secreted protein Slit repels neuronal precursors migrating from the anterior subventricular zone in the telencephalon to the olfactory bulb. Our results provide a di...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/22477
更新日期：1999-07-22 00:00:00
abstract：:The retina in most mammals contains two types of macroglial cells--Müller cells, which span the entire thickness of the retina, and astrocytes, which are mainly confined to the nerve fibre layer. Whereas Müller cells are diffusely distributed in all vertebrate retinae, the presence and distribution of retinal astrocyt...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/332834a0
更新日期：1988-04-28 00:00:00
abstract：:Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metaz...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature08140
更新日期：2009-07-16 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41586-020-2064-8
更新日期：2020-03-01 00:00:00
abstract：:AFTER exposure to secretagogues the small intestine changes from a tissue that absorbs fluid and electrolyte from lumen to blood into a tissue that secretes electrolyte and fluid into the lumen(1-4). It has been shown that this secretion results from an increase in the passive Cl(-) permeability of the mucosal border,...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/279446a0
更新日期：1979-05-31 00:00:00
abstract：:Self-assembled polyhedral structures are common in biology. The coats of many viruses, for example, have a structure based on icosahedral symmetry. The preparation of synthetic polyhedral molecular assemblies represents a challenging problem, but supramolecular chemistry has now advanced to the point where the task ma...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/19740
更新日期：1999-04-29 00:00:00
abstract：:Surface gravity is a basic stellar property, but it is difficult to measure accurately, with typical uncertainties of 25 to 50 per cent if measured spectroscopically and 90 to 150 per cent if measured photometrically. Asteroseismology measures gravity with an uncertainty of about 2 per cent but is restricted to relati...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature12419
更新日期：2013-08-22 00:00:00
abstract：:Sex and recombination are widespread, but explaining these phenomena has been one of the most difficult problems in evolutionary biology. Recombination is advantageous when different individuals in a population carry different advantageous alleles. By bringing together advantageous alleles onto the same chromosome, re...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05049
更新日期：2006-09-07 00:00:00
abstract：:The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature12862
更新日期：2014-01-30 00:00:00
abstract：:The maternal gene bicoid (bcd) determines pattern in the anterior half of the Drosophila embryo. It is reported here that the injection of bcd mutant embryos with messenger RNAs that encode proteins consisting of heterologous acidic transcriptional activating sequences fused to the DNA-binding portion of the bcd gene ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/342149a0
更新日期：1989-11-09 00:00:00
abstract：:The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35097083
更新日期：2001-10-04 00:00:00
abstract：:Emerging infectious diseases present a formidable challenge to the conservation of native species in the twenty-first century. Diseases caused by introduced pathogens have had large impacts on species abundances, including the American chestnut, Hawaiian bird species and many amphibians. Changes in host population siz...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05829
更新日期：2007-06-07 00:00:00
abstract：:Some beetles in the Namib Desert collect drinking water from fog-laden wind on their backs. We show here that these large droplets form by virtue of the insect's bumpy surface, which consists of alternating hydrophobic, wax-coated and hydrophilic, non-waxy regions. The design of this fog-collecting structure can be re...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35102108
更新日期：2001-11-01 00:00:00
abstract：:The CD4 subset of cells displays helper/inducer activity and recognizes class II antigens of the major histocompatibility complex (MHC), while the CD8 subset recognizes class I MHC antigens and exhibits cytotoxic or suppressor function. Considerable functional as well as corresponding phenotypic heterogeneity exists w...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/330479a0
更新日期：1987-12-03 00:00:00
abstract：:Gigantopithecus blacki was a giant hominid that inhabited densely forested environments of Southeast Asia during the Pleistocene epoch1. Its evolutionary relationships to other great ape species, and the divergence of these species during the Middle and Late Miocene epoch (16-5.3 million years ago), remain unclear2,3....
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1728-8
更新日期：2019-12-01 00:00:00
abstract：:A human myelomonocytic cell line, U937, produced an interleukin-1 (IL-1) receptor antagonist protein (IRAP) which was purified and partially sequenced. A complementary DNA coding for IRAP was cloned and sequenced. The mature translation product of the cDNA has been expressed in Escherichia coli and was an active compe...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/344633a0
更新日期：1990-04-12 00:00:00
abstract：:During intracellular Ca2+ signalling mitochondria accumulate significant amounts of Ca2+ from the cytosol. Mitochondrial Ca2+ uptake controls the rate of energy production, shapes the amplitude and spatio-temporal patterns of intracellular Ca2+ signals, and is instrumental to cell death. This Ca2+ uptake is undertaken...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02246
更新日期：2004-01-22 00:00:00
abstract：:Photosynthetic dinoflagellates are important aquatic primary producers and notorious causes of toxic 'red tides'. Typical dinoflagellate chloroplasts differ from all other plastids in having a combination of three envelope membranes and peridinin-chlorophyll a/c light-harvesting pigments. Despite evidence of a dinofla...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/22099
更新日期：1999-07-08 00:00:00
abstract：:The tuatara (Sphenodon punctatus)-the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2-is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2561-9
更新日期：2020-08-01 00:00:00
abstract：:Scientific fraud, much in the news recently, is not a new phenomenon. What follows is a personal account of a particular case. ...
journal_title：Nature
pub_type： 传,历史文章,杂志文章
doi：10.1038/357434a0
更新日期：1992-06-11 00:00:00
abstract：:The plant hormone auxin is central in many aspects of plant development. Previous studies have implicated the ubiquitin-ligase SCF(TIR1) and the AUX/IAA proteins in auxin response. Dominant mutations in several AUX/IAA genes confer pleiotropic auxin-related phenotypes, whereas recessive mutations affecting the functio...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35104500
更新日期：2001-11-15 00:00:00
abstract：:The first zygotic genes to be expressed during early Drosophila development are the gap genes. Their role is to read and interpret coarse positional information deposited in the egg by the mother and to refine it by cross-regulatory interactions and by controlling a class of pair-rule genes. Little is known about the ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/341335a0
更新日期：1989-09-28 00:00:00
abstract：:We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on exter...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/317145a0
更新日期：1985-09-12 00:00:00
abstract：:Retroviral integration is catalysed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome. How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foamy virus (PFV) intasome ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature14495
更新日期：2015-07-16 00:00:00
