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 advent of endothermy, which is achieved through the continuous homeostatic regulation of body temperature and metabolism1,2, is a defining feature of mammalian and avian evolution. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conser...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2387-5
更新日期:2020-07-01 00:00:00
abstract::In Drosophila, Decapentaplegic (Dpp) and Wingless (Wg) are two secreted signalling proteins of the transforming growth factor (TGF)-beta and Wnt families, respectively. Although both are often required during development, only a few downstream components of these signalling pathways have been described. Here we presen...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/383630a0
更新日期:1996-10-17 00:00:00
abstract::Hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) produces two prospective intracellular messengers: inositol 1,4,5-trisphosphate (InsP3), which releases Ca2+ from intracellular stores; and diacylglycerol (DG), which activates protein kinase C. Here we show how the formation...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/323333a0
更新日期:1986-09-25 00:00:00
abstract::In Drosophila, as in mammals, epidermal differentiation is controlled by signalling cascades that include Wnt proteins and the ovo/shavenbaby (svb) family of zinc-finger transcription factors. Ovo/svb is a complex gene with two genetic functions corresponding to separate control regions: ovo is required for female ger...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/22330
更新日期:1999-07-15 00:00:00
abstract::Lake Victoria, together with its satellite lakes, harbours roughly 200 endemic forms of cichlid fishes that are classified as 'haplochromines' and yet the lake system is less than a million years old. This 'flock' has attracted attention because of the possibility that it evolved within the lake from one ancestral spe...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/347550a0
更新日期:1990-10-11 00:00:00
abstract::The architecture of trabecular bone, the porous bone found in the spine and at articulating joints, provides the requirements for optimal load transfer, by pairing suitable strength and stiffness to minimal weight according to rules of mathematical design. But, as it is unlikely that the architecture is fully pre-prog...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35015116
更新日期:2000-06-08 00:00:00
abstract::Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates. The specific physical mechanisms responsible for generating those emissions are not well understood, but in general the spot seems to arise because of an elec...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415997a
更新日期:2002-02-28 00:00:00
abstract::A complex between HLA-DR3 and a fragment of invariant chain called CLIP was isolated from a human cell line defective in antigen presentation and its X-ray crystal structure determined. Previous data indicate that this complex is an intermediate in class II histocompatibility maturation, occurring between invariant ch...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/378457a0
更新日期:1995-11-30 00:00:00
abstract::Ligand-gated ion channels are multi-subunit complexes where each subunit-type is encoded by several related genes. Heterologous expression of any one of the neuronal nicotinic acetylcholine receptors (nAChR) alpha-type subunits, either alone or with any beta-type subunit, typically yields functional nAChR channels. A ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380347a0
更新日期:1996-03-28 00:00:00
abstract::State-of-the-art optical clocks1 achieve precisions of 10-18 or better using ensembles of atoms in optical lattices2,3 or individual ions in radio-frequency traps4,5. Promising candidates for use in atomic clocks are highly charged ions6 (HCIs) and nuclear transitions7, which are largely insensitive to external pertur...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2221-0
更新日期:2020-05-01 00:00:00
abstract::Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conf...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03798
更新日期:2005-07-21 00:00:00
abstract::The primary structure of the poliovirus genome has been determined. The RNA molecule is 7,433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2,207 consecutive triplets spans over 89% of the nucleotide sequence and codes f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/291547a0
更新日期:1981-06-18 00:00:00
abstract::Recent work has identified a neuron with widespread projections to odour processing regions of the honeybee brain whose activity represents the reward value of gustatory stimuli. We have constructed a model of bee foraging in uncertain environments based on this type of neuron and a predictive form of hebbian synaptic...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/377725a0
更新日期:1995-10-26 00:00:00
abstract::There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approxima...
journal_title:Nature
pub_type: 杂志文章,多中心研究
doi:10.1038/nature05911
更新日期:2007-06-07 00:00:00
abstract::There is increasing evidence for the process of sympatric speciation, in which reproductive isolation of species occurs without physical isolation. Theoretical models have focused on disruptive natural selection as the crucial pressure for splitting a species. Here we report the theoretical finding that sympatric spec...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/990087
更新日期:1999-12-02 00:00:00
abstract::The innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12640
更新日期:2013-11-28 00:00:00
abstract::Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, inc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/381251a0
更新日期:1996-05-16 00:00:00
abstract::Epstein-Barr virus (EBV), a member of the herpes group of viruses and the aetiological agent of infectious mononucleosis, is usually thought of as a lymphotrophic virus with the ability to transform B lymphocytes. So the association of EBV with nasopharyngeal carcinoma is puzzling, especially given the lack of success...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306480a0
更新日期:1983-12-01 00:00:00
abstract::Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12437
更新日期:2013-09-19 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::Oligodendrocytes and astrocytes are macroglial cells of the vertebrate central nervous system. These cells have diverse roles in the maintenance of neurological function. In the embryo, the genetic mechanisms that underlie the specification of macroglial precursors in vivo appear strikingly similar to those that regul...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature09611
更新日期:2010-11-11 00:00:00
abstract::Simple mathematical models of the transmission dynamics of human immunodeficiency virus help to clarify some of the essential relations between epidemiological factors, such as distributed incubation periods and heterogeneity in sexual activity, and the overall pattern of the AIDS epidemic. They also help to identify ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/326137a0
更新日期:1987-03-12 00:00:00
abstract::The ability of mass spectrometry to generate intact biomolecular ions efficiently in the gas phase has led to its widespread application in metabolomics, proteomics, biological imaging, biomarker discovery and clinical assays (namely neonatal screens). Matrix-assisted laser desorption/ionization (MALDI) and electrospr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06195
更新日期:2007-10-25 00:00:00
abstract::Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0043-0
更新日期:2018-04-01 00:00:00
abstract::Although it has been proposed that the activation of T lymphocytes is mediated by an early rise in cytosolic calcium concentration, it has not been possible to mimic antigen- or mitogen-induced mouse lymphocyte activation by calcium ionophores that bypass receptor-mediated processes. There is now evidence from other s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/313318a0
更新日期:1985-01-24 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-018-07240-0
更新日期:2018-11-01 00:00:00
abstract::The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS). In addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence suggests the existence of additional inhibitors in CNS myelin. We show here that a ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature00867
更新日期:2002-06-27 00:00:00
abstract::The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature20576
更新日期:2016-12-22 00:00:00
abstract::Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented. The absence of crown catarrhine fossils older than ∼20 million years (Myr) has stood in stark contrast to molecular divergence estimates ...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature12161
更新日期:2013-05-30 00:00:00
abstract::Magnetic surveys of the martian surface have revealed significantly lower magnetic field intensities over the gigantic impact craters Hellas and Argyre than over surrounding regions. The reduced fields are commonly attributed to pressure demagnetization caused by shock waves generated during meteorite impact, in the a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03560
更新日期:2005-05-12 00:00:00