Abstract:
:p53 is the most frequently mutated gene in human cancers and mutant p53 has a gain of function (GOF) that promotes tumor progression and therapeutic resistance. One of the major GOF activities of mutant p53 is to suppress 2 other p53 family proteins, p63 and p73. However, the molecular basis is not fully understood. Here, we examined whether mutant p53 antagonizes p63/p73-mediated tumor suppression in vivo by using mutant p53-R270H knockin and TAp63/p73-deficient mouse models. We found that knockin mutant p53-R270H shortened the life span of p73 +/- mice and subjected TAp63 +/- or p73 +/- mice to T lymphoblastic lymphomas (TLBLs). To unravel the underlying mechanism, we showed that mutant p53 formed a complex with Notch1 intracellular domain (NICD) and antagonized p63/p73-mediated repression of HES1 and ECM1. As a result, HES1 and ECM1 were overexpressed in TAp63 +/- ;p53 R270H/- and p73 +/- ;p53 R270H/- TLBLs, suggesting that normal function of HES1 and ECM1 in T cell activation is hyperactivated, leading to lymphomagenesis. Together, our data reveal a previously unappreciated mechanism by which GOF mutant p53 hijacks the p63/p73-regulated transcriptional program via the Notch1 pathway.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhang J,Sun W,Kong X,Zhang Y,Yang HJ,Ren C,Jiang Y,Chen M,Chen Xdoi
10.1073/pnas.1913919116subject
Has Abstractpub_date
2019-11-26 00:00:00pages
24259-24267issue
48eissn
0027-8424issn
1091-6490pii
1913919116journal_volume
116pub_type
杂志文章abstract::The chemical dynamics of lakes and streams affect their suitability as aquatic habitats and as water supplies for human needs. Because water quality is typically monitored only weekly or monthly, however, the higher-frequency dynamics of stream chemistry have remained largely invisible. To illuminate a wider spectrum ...
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.1304328110
更新日期:2013-07-23 00:00:00
abstract::Two forms of lactoferrin, an intact lactoferrin and a "nicked" but apparently intact (i.e., 78-kDa) form, have been isolated from the urine of preterm infants fed human milk. These two forms of lactoferrin, demonstrated to be entirely of maternal origin, were copurified using affinity columns of immobilized single-str...
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.88.8.2994
更新日期:1991-04-15 00:00:00
abstract::Antigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-gamma, -delta, -epsilon, and -zeta. The mouse CD3-gamma gene, consisting of seven exons, was found to be highly homologous to the CD3-delta gene described earlier. Both the high level of sequence h...
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.84.24.9131
更新日期:1987-12-01 00:00:00
abstract::Excitatory amino acid transporters (EAATs) buffer and remove synaptically released L-glutamate and maintain its concentrations below neurotoxic levels. EAATs also mediate a thermodynamically uncoupled substrate-gated anion conductance that may modulate cell excitability. Here, we demonstrate that modification of a cys...
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.011400198
更新日期:2001-12-18 00:00:00
abstract::The charge-stabilization effect associated with alpha-helices in proteins has been reexamined by microscopic calculations without any a priori assumptions about the dielectric constant of the protein. The calculations reproduce the observed charge stabilization effect of a helix in two well-defined test cases: a histi...
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.88.5.2026
更新日期:1991-03-01 00:00:00
abstract::Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a crossreactive idiotype on 48% of human IgM RF paraproteins, but does not re...
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.84.9.2916
更新日期:1987-05-01 00:00:00
abstract::A single anterior-animal blastomere, which includes the presumptive neural region in the eight-cell embryo of the Halocynthia, a protochordate, when dissociated, cleavage-arrested with cytochalasin B, and cultured in isolation, differentiated exclusively to epidermal type judging from membrane excitability and immunor...
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.85.16.6197
更新日期:1988-08-01 00:00:00
abstract::Integral membrane proteins that form water-filled channels through membranes often exist as aggregates of similar or identical subunits spanning the membrane. It has been suggested that the insertion into the membrane of the channel-forming domains of the subunits may impart unusual structural features to the membrane...
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.82.4.958
更新日期:1985-02-01 00:00:00
abstract::The output of the cerebellar cortex is controlled by two main inputs, (i.e., the climbing fiber and mossy fiber-parallel fiber pathway) and activations of these inputs elicit characteristic effects in its Purkinje cells: that is, the so-called complex spikes and simple spikes. Target neurons of the Purkinje cells in t...
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.0907118107
更新日期:2010-05-04 00:00:00
abstract::Mutations of esterase 3 confer two forms of organophosphate resistance on contemporary Australasian Lucilia cuprina. One form, called diazinon resistance, is slightly more effective against commonly used insecticides and is now more prevalent than the other form, called malathion resistance. We report here that the si...
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.0509590103
更新日期:2006-06-06 00:00:00
abstract::The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A-retinol-binding protein complex. Mutations 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.1121005109
更新日期:2012-06-12 00:00:00
abstract::Complex phenotypes can be modeled as networks of component traits connected by genetic, developmental, or functional interactions. Aposematism, which has evolved multiple times in poison frogs (Dendrobatidae), links a warning signal to a chemical defense against predators. Other traits are involved in this complex phe...
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.1010952108
更新日期:2011-04-12 00:00:00
abstract::Many first-line cancer drugs are natural products or are derived from them by chemical modification. The trioxacarcins are an emerging class of molecules of microbial origin with potent antiproliferative effects, which may derive from their ability to covalently modify duplex DNA. All trioxacarcins appear to be deriva...
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.1015257108
更新日期:2011-04-26 00:00:00
abstract::The results of normal-mode analyses are in accord with the proposal that a low-frequency motion of the HhaI methyltransferase enzyme is responsible for base flipping in bound DNA. The vectors of the low-frequency normal mode of residues Ser-85 and Ile-86 point directly to the phosphate and ribose moieties of the DNA b...
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.0507913102
更新日期:2005-11-08 00:00:00
abstract::Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in s...
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.0905063106
更新日期:2009-11-03 00:00:00
abstract::In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had ...
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.0502762102
更新日期:2005-08-30 00:00:00
abstract::Sialic acid-containing glycosphingolipids, i.e., gangliosides, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose:ceramide glucosyltransferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. To gain insight into the role of GSLs 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.0500893102
更新日期:2005-08-30 00:00:00
abstract::Phosphorylation of ADP to ATP was induced in nonrespiring submitochondrial particles (SMP) from rat liver by the application of electric pulses with field strengths of 10-35 kV/cm and a decay time of 60 mus. In all cases respiration was inhibited completely by using cyanide or rotenone. Newly formed ATP was measured b...
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.78.12.7473
更新日期:1981-12-01 00:00:00
abstract::Marine Archaea are important players among microbial plankton and significantly contribute to biogeochemical cycles, but details regarding their community structure and long-term seasonal activity and dynamics remain largely unexplored. In this study, we monitored the interannual archaeal community composition of abun...
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.1216863110
更新日期:2013-04-09 00:00:00
abstract::Paleoanthropologists and vertebrate paleontologists have for decades debated the etiology of tooth wear and its implications for understanding the diets of human ancestors and other extinct mammals. The debate has recently taken a twist, calling into question the efficacy of dental microwear to reveal diet. Some argue...
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.1509491112
更新日期:2015-08-25 00:00:00
abstract::Germ-line mutations of the BRCA2 tumor suppressor gene greatly increase the risk of developing breast and ovarian cancers. Here, we show that wild-type BRCA2, but not a tumor-specific truncated mutant BRCA2, synergizes with the nuclear receptor coactivator p160 GRIP1 to enhance transcriptional activation by androgen r...
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.1132020100
更新日期:2003-06-10 00:00:00
abstract::A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (...
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.0907511106
更新日期:2009-11-24 00:00:00
abstract::Recent analyses of high-throughput protein interaction data coupled with large-scale investigations of evolutionary properties of interaction networks have left some unanswered questions. To what extent do protein interactions act as constraints during evolution of the protein sequence? How does the type of interactio...
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.0502667102
更新日期:2005-08-02 00:00:00
abstract::The 30S ribosomal subunit of E. coli was treated with the bifunctional reagent bis-(methyl)suberimidate. Crosslinked ribosomal proteins were identified as bands with increased molecular weight after electrophoresis in polyacrylamide gels containing sodium dodecyl sulphate. The pattern of crosslinked products was alter...
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.69.5.1327
更新日期:1972-05-01 00:00:00
abstract::A perversion in an otherwise uniform helical structure, such as a climbing plant tendril, refers to a kink that connects two helices with opposite chiralities. Such singularity structures are widely seen in natural and artificial mechanical systems, and they provide the fundamental mechanism of helical symmetry breaki...
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.1605621113
更新日期:2016-06-28 00:00:00
abstract::Listeriolysin O (LLO) is a cholesterol-dependent cytolysin that is an essential virulence factor of Listeria monocytogenes. LLO pore-forming activity is pH-dependent; it is active at acidic pH (<6), but not at neutral pH. In contrast to other pH-dependent toxins, we have determined that LLO pore-forming activity is co...
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.0500558102
更新日期:2005-08-30 00:00:00
abstract::An ammonia-oxidizing, carbon-fixing archaeon, Candidatus "Nitrosopumilus maritimus," recently was isolated from a salt-water aquarium, definitively confirming that chemoautotrophy exists among the marine archaea. However, in other incubation studies, pelagic archaea also were capable of using organic carbon. It has re...
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.0510157103
更新日期:2006-04-25 00:00:00
abstract::Residential location is thought to influence people's well-being, but different individuals may value residential areas differently. We examined how life satisfaction and personality traits are geographically distributed within the UK London metropolitan area, and how the strength of associations between personality t...
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.1415800112
更新日期:2015-01-20 00:00:00
abstract::Therapeutic cancer vaccines can be effective for treating patients, but clinical responses vary considerably from patient to patient. Early indicators of a favorable response are crucial for making individualized treatment decisions and advancing vaccine design, but no validated biomarkers are currently available. In ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1073/pnas.1314722111
更新日期:2014-04-29 00:00:00
abstract::Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemotherapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platin...
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.84.23.8225
更新日期:1987-12-01 00:00:00