Abstract：
:The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); however, the mechanism by which PML regulates Mdm2 remains unclear. Here, we show that PML enhances p53 stability by sequestering Mdm2 to the nucleolus. We found that after DNA damage, PML and Mdm2 accumulate in the nucleolus in an Arf-independent manner. In addition, we found that the nucleolar localization of PML is dependent on ATR activation and phosphorylation of PML by ATR. Notably, in Pml(-/-) cells, sequestration of Mdm2 to the nucleolus was impaired, as well as p53 stabilization and the induction of apoptosis. Furthermore, we demonstrate that PML physically associates with the nucleolar protein L11, and that L11 knockdown impairs the ability of PML to localize to nucleoli after DNA damage. These findings demonstrate an unexpected role of PML in the nucleolar network for tumour suppression.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Bernardi R,Scaglioni PP,Bergmann S,Horn HF,Vousden KH,Pandolfi PPdoi
10.1038/ncb1147keywords:
subject
Has Abstractpub_date
2004-07-01 00:00:00pages
665-72issue
7eissn
1465-7392issn
1476-4679pii
ncb1147journal_volume
6pub_type
杂志文章abstract：:Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a mod...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1787
更新日期：2008-11-01 00:00:00
abstract：:Here we show that segregation of homologous chromosomes and that of sister chromatids are differentially regulated in Xenopus and possibly in other higher eukaryotes. Upon hormonal stimulation, Xenopus oocytes microinjected with antibodies against the anaphase-promoting complex (APC) activator Fizzy or the APC core su...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35050607
更新日期：2001-01-01 00:00:00
abstract：:Understanding the factors that direct tissue organization during development is one of the most fundamental goals in developmental biology. Various hypotheses explain cell sorting and tissue organization on the basis of the adhesive and mechanical properties of the constituent cells. However, validating these hypothes...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1705
更新日期：2008-04-01 00:00:00
abstract：:Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bi...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2879
更新日期：2013-12-01 00:00:00
abstract：:Cholesterol is a structural component of animal membranes that influences fluidity, permeability and formation of lipid microdomains. It is also a precursor to signalling molecules, including mammalian steroid hormones and insect ecdysones. The nematode Caenorhabditis elegans requires too little cholesterol for it to ...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb0803-684
更新日期：2003-08-01 00:00:00
abstract：:Activation of mitosis-promoting factor (MPF) drives mitotic commitment. In human cells active MPF appears first on centrosomes. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation dri...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2633
更新日期：2013-01-01 00:00:00
abstract：:Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the cir...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3094
更新日期：2015-02-01 00:00:00
abstract：:The serine/threonine protein kinase Akt is involved in a variety of cellular processes including cell proliferation, survival, metabolism and gene expression. It is essential in vascular endothelial growth factor (VEGF)-mediated angiogenesis; however, it is not known how Akt regulates the migration of endothelial cell...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1695
更新日期：2008-03-01 00:00:00
abstract：:Hypoxia and acidosis occur in a wide variety of physiological and pathological settings that include muscle stress, tumour development and ischaemic disorders. A central element in the adaptive response to cellular hypoxia is HIF (hypoxia-inducible factor), a transcription factor that activates an array of genes impli...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1144
更新日期：2004-07-01 00:00:00
abstract：:The physical characteristics of tumours are intricately linked to the tumour phenotype and difficulties during treatment. Many factors contribute to the increased stiffness of tumours; from increased matrix deposition, matrix remodelling by forces from cancer cells and stromal fibroblasts, matrix crosslinking, increas...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/s41556-018-0131-2
更新日期：2018-07-01 00:00:00
abstract：:The planar cell polarity (PCP) signalling pathway is essential for embryonic development because it governs diverse cellular behaviours, and 'core PCP' proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the 'PCP effector' proteins, such as Intu and Fuz, remain largely unstudi...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1966
更新日期：2009-10-01 00:00:00
abstract：:The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and position of the mitotic spindle. In the Drosophila embryo, the determinant Prospero is localized basally and is segregated equally to daughters of similar cell size during ep...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/71323
更新日期：2000-01-01 00:00:00
abstract：:The enteric nervous system (ENS) predominantly originates from vagal neural crest (VNC) cells that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhanc...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0428-9
更新日期：2019-12-01 00:00:00
abstract：:Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb746
更新日期：2002-02-01 00:00:00
abstract：:Although many genes that lead to different types of cancer when mutated have been identified, the cells that initiate tumour formation following accumulation of these mutations have, until recently, remained elusive. This review explores how mouse genetic lineage-tracing experiments that allow the expression of oncoge...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2657
更新日期：2013-02-01 00:00:00
abstract：:Individual neurons form specific elaborate dendritic structures that receive presynaptic information. The pattern of dendritic branching is regulated by the microtubule-associated motor protein dynein, which is responsible for the transport of essential endosomes and other organelles into the dendrites. ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb1008-1131
更新日期：2008-10-01 00:00:00
abstract：:Mammalian and most fungal infectious proteins (also known as prions) are self-propagating amyloid, a filamentous beta-sheet structure. A prion domain determines the infectious properties of a protein by forming the core of the amyloid. We compare the properties of known prion domains and their interactions with the re...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb1105-1039
更新日期：2005-11-01 00:00:00
abstract：:Given the important role of the hypothalamus in regulating feeding and metabolism, there has been considerable interest in a possible function for hypothalamic stem cells in modulating body weight in health and disease. Mice given a high-fat diet develop inflammation in the hypothalamus and lose key types of neurons. ...
journal_title：Nature cell biology
pub_type： 新闻
doi：10.1038/ncb2599
更新日期：2012-10-01 00:00:00
abstract：:Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1905
更新日期：2009-08-01 00:00:00
abstract：:The cytokine tumour necrosis factor (TNF) and the toll-like receptors (TLRs) coordinate immune responses by activating inflammatory transcriptional programs, but these signals can also trigger cell death. Recent studies identify the MAP kinase substrate MK2 as a key player in determining whether cells live or die in r...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3619
更新日期：2017-09-29 00:00:00
abstract：:Chromatin structure is thought to play a critical role in gene expression. Using the lac operator/repressor system and two colour variants of green fluorescent protein (GFP), we developed a system to visualize a gene and its protein product directly in living cells, allowing us to examine the spatial organization and ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35046510
更新日期：2000-12-01 00:00:00
abstract：:Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2048
更新日期：2010-05-01 00:00:00
abstract：:NMDA (N-methyl-D-aspartate) receptors (NMDARs) are targeted to dendrites and anchored at the post-synaptic density (PSD) through interactions with PDZ proteins. However, little is known about how these receptors are sorted from the endoplasmic reticulum and Golgi apparatus to the synapse. Here, we find that synapse-as...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb990
更新日期：2003-06-01 00:00:00
abstract：:The precise regulation of growth factor signalling is crucial to the molecular control of development in Drosophila. Post-translational modification of signalling molecules is one of the mechanisms that modulate developmental signalling specificity. We describe a new gene, fringe connection (frc), that encodes a nucle...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb0901-809
更新日期：2001-09-01 00:00:00
abstract：:Pumilio proteins PUM1 and PUM2 are shown to regulate microRNA-dependent gene silencing by induction of a conformational switch in the 3' untranslated region of p27 mRNA. This conformational change is required for efficient microRNA-mediated repression of this cell-cycle regulator in rapidly proliferating cells. ...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb1010-928
更新日期：2010-10-01 00:00:00
abstract：:The pericentriolar material (PCM), the microtubule-organizing component of the centrosome, contains a multitude of proteins and is commonly described as an amorphous cloud surrounding the centrioles. However, the days of the PCM as an unstructured matrix are numbered. Using super-resolution microscopy, several reports...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2617
更新日期：2012-11-01 00:00:00
abstract：:The GTPase dynamin plays an essential part in endocytosis by catalysing the fission of nascent clathrin-coated vesicles from the plasma membrane. Using preformed phosphatidylinositol-4,5-bisphosphate-containing lipid nanotubes as a membrane template for dynamin self-assembly, we investigate the conformational changes ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/8997
更新日期：1999-05-01 00:00:00
abstract：:Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification. Multipolar-spindle conformation favours incorrect kinetochore-microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability. Spindle-pole organization influences and is infl...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2423
更新日期：2012-02-05 00:00:00
abstract：:The Notch1 gene has an important role in mammalian cell-fate decision and tumorigenesis. Upstream control mechanisms for transcription of this gene are still poorly understood. In a chemical genetics screen for small molecule activators of Notch signalling, we identified epidermal growth factor receptor (EGFR) as a ke...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1750
更新日期：2008-08-01 00:00:00
abstract：:Although nuclear envelope (NE) assembly is known to require the GTPase Ran, the membrane fusion machinery involved is uncharacterized. NE assembly involves formation of a reticular network on chromatin, fusion of this network into a closed NE and subsequent expansion. Here we show that p97, an AAA-ATPase previously im...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1201-1086
更新日期：2001-12-01 00:00:00
