当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.

Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.

Abstract：

:The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of low-molecular-weight compounds in order to identify compounds that can restore wild-type function to mutant p53. We found one compound capable of inducing apoptosis in human tumor cells through restoration of the transcriptional transactivation function to mutant p53. This molecule, named PRIMA-1, restored sequence-specific DNA binding and the active conformation to mutant p53 proteins in vitro and in living cells. PRIMA-1 rescued both DNA contact and structural p53 mutants. In vivo studies in mice revealed an antitumor effect with no apparent toxicity. This molecule may serve as a lead compound for the development of anticancer drugs targeting mutant p53.

journal_name

Nat Med

journal_title

Nature medicine

authors

Bykov VJ,Issaeva N,Shilov A,Hultcrantz M,Pugacheva E,Chumakov P,Bergman J,Wiman KG,Selivanova G

doi

10.1038/nm0302-282

keywords:

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

282-8

issue

3

eissn

1078-8956

issn

1546-170X

pii

nm0302-282

journal_volume

8

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

    abstract：:Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4055

    authors： Camarda R,Zhou AY,Kohnz RA,Balakrishnan S,Mahieu C,Anderton B,Eyob H,Kajimura S,Tward A,Krings G,Nomura DK,Goga A

    更新日期：2016-04-01 00:00:00

  • Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity.

    abstract：:A variable region gene of the T-cell receptor, V beta 8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2u mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding V beta 8.2 protecte...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0896-899

    authors： Waisman A,Ruiz PJ,Hirschberg DL,Gelman A,Oksenberg JR,Brocke S,Mor F,Cohen IR,Steinman L

    更新日期：1996-08-01 00:00:00

  • HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

    abstract：:HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their H...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1197-1250

    authors： Mazzoli S,Trabattoni D,Lo Caputo S,Piconi S,Blé C,Meacci F,Ruzzante S,Salvi A,Semplici F,Longhi R,Fusi ML,Tofani N,Biasin M,Villa ML,Mazzotta F,Clerici M

    更新日期：1997-11-01 00:00:00

  • Akt2 relaxes podocytes in chronic kidney disease.

    abstract：:A signaling cascade is activated in podocytes to induce survival and cope with stress during advanced glomerular disease, a new study shows. The findings may also explain why the immunosuppressor sirolimus, an inhibitor of this pathway, can cause proteinuria in a subset of patients with chronic kidney disease (pages 1...

    journal_title：Nature medicine

    pub_type： 评论,新闻

    doi：10.1038/nm.3357

    authors： Reiser J

    更新日期：2013-10-01 00:00:00

  • Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.

    abstract：:Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3751

    authors： Yoda A,Adelmant G,Tamburini J,Chapuy B,Shindoh N,Yoda Y,Weigert O,Kopp N,Wu SC,Kim SS,Liu H,Tivey T,Christie AL,Elpek KG,Card J,Gritsman K,Gotlib J,Deininger MW,Makishima H,Turley SJ,Javidi-Sharifi N,Maciejewski

    更新日期：2015-01-01 00:00:00

  • A GABAergic system in airway epithelium is essential for mucus overproduction in asthma.

    abstract：:Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic aci...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1604

    authors： Xiang YY,Wang S,Liu M,Hirota JA,Li J,Ju W,Fan Y,Kelly MM,Ye B,Orser B,O'Byrne PM,Inman MD,Yang X,Lu WY

    更新日期：2007-07-01 00:00:00

  • Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo.

    abstract：:Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2847

    authors： Yipp BG,Petri B,Salina D,Jenne CN,Scott BN,Zbytnuik LD,Pittman K,Asaduzzaman M,Wu K,Meijndert HC,Malawista SE,de Boisfleury Chevance A,Zhang K,Conly J,Kubes P

    更新日期：2012-09-01 00:00:00

  • Protective immunity from a germinal center sanctuary.

    abstract：:A new study provides mechanistic insights into how live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) can protect monkeys from infection with pathogenic SIV. The authors show that replicating LAVs stimulate a protective immune response from a safe haven in the germinal centers of lymph nodes (pages 16...

    journal_title：Nature medicine

    pub_type： 评论,杂志文章

    doi：10.1038/nm.2986

    authors： Robinson HL,Amara RR

    更新日期：2012-11-01 00:00:00

  • Real-time quantitative RT-PCR after laser-assisted cell picking.

    abstract：:The present study describes a technique for quantitation of mRNA in a few isotypic cells obtained from an intact organ structure by combining laser-assisted cell picking and real-time PCR. The microscopically controlled lasering of selected cells in stained tissue sections was applied to lung alveolar macrophages, whi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/3327

    authors： Fink L,Seeger W,Ermert L,Hänze J,Stahl U,Grimminger F,Kummer W,Bohle RM

    更新日期：1998-11-01 00:00:00

  • Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

    abstract：:Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0402-349

    authors： Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

    更新日期：2002-04-01 00:00:00

  • Wearable sensor data and self-reported symptoms for COVID-19 detection.

    abstract：:Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-1123-x

    authors： Quer G,Radin JM,Gadaleta M,Baca-Motes K,Ariniello L,Ramos E,Kheterpal V,Topol EJ,Steinhubl SR

    更新日期：2021-01-01 00:00:00

  • Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough.

    abstract：:Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is u...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0796-814

    authors： Fox AJ,Lalloo UG,Belvisi MG,Bernareggi M,Chung KF,Barnes PJ

    更新日期：1996-07-01 00:00:00

  • A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography.

    abstract：:Improved techniques to noninvasively image protein-protein interactions (PPIs) are essential. We molecularly engineered a positron emission tomography (PET)-based split reporter (herpes simplex virus type 1 thymidine kinase), cleaved between Thr265 and Ala266, and used this in a protein-fragment complementation assay ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2185

    authors： Massoud TF,Paulmurugan R,Gambhir SS

    更新日期：2010-08-01 00:00:00

  • Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1.

    abstract：:Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3142

    authors： Gebeshuber CA,Kornauth C,Dong L,Sierig R,Seibler J,Reiss M,Tauber S,Bilban M,Wang S,Kain R,Böhmig GA,Moeller MJ,Gröne HJ,Englert C,Martinez J,Kerjaschki D

    更新日期：2013-04-01 00:00:00

  • Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress.

    abstract：:Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/82168

    authors： Yan SF,Fujita T,Lu J,Okada K,Shan Zou Y,Mackman N,Pinsky DJ,Stern DM

    更新日期：2000-12-01 00:00:00

  • A cannabinoid mechanism in relapse to cocaine seeking.

    abstract：:Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstat...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1001-1151

    authors： De Vries TJ,Shaham Y,Homberg JR,Crombag H,Schuurman K,Dieben J,Vanderschuren LJ,Schoffelmeer AN

    更新日期：2001-10-01 00:00:00

  • The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

    abstract：:The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3974

    authors： Miner JJ,Daniels BP,Shrestha B,Proenca-Modena JL,Lew ED,Lazear HM,Gorman MJ,Lemke G,Klein RS,Diamond MS

    更新日期：2015-12-01 00:00:00

  • Studying clonal dynamics in response to cancer therapy using high-complexity barcoding.

    abstract：:Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3841

    authors： Bhang HE,Ruddy DA,Krishnamurthy Radhakrishna V,Caushi JX,Zhao R,Hims MM,Singh AP,Kao I,Rakiec D,Shaw P,Balak M,Raza A,Ackley E,Keen N,Schlabach MR,Palmer M,Leary RJ,Chiang DY,Sellers WR,Michor F,Cooke VG,Korn JM

    更新日期：2015-05-01 00:00:00

  • Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

    abstract：:Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1097-1150

    authors： Vígh L,Literáti PN,Horváth I,Török Z,Balogh G,Glatz A,Kovács E,Boros I,Ferdinándy P,Farkas B,Jaszlits L,Jednákovits A,Korányi L,Maresca B

    更新日期：1997-10-01 00:00:00

  • Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment.

    abstract：:In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3822

    authors： Marquard J,Otter S,Welters A,Stirban A,Fischer A,Eglinger J,Herebian D,Kletke O,Klemen MS,Stožer A,Wnendt S,Piemonti L,Köhler M,Ferrer J,Thorens B,Schliess F,Rupnik MS,Heise T,Berggren PO,Klöcker N,Meissner T,Ma

    更新日期：2015-04-01 00:00:00

  • Vaccines: past, present and future.

    abstract：:The vaccines developed over the first two hundred years since Jenner's lifetime have accomplished striking reductions of infection and disease wherever applied. Pasteur's early approaches to vaccine development, attenuation and inactivation, are even now the two poles of vaccine technology. Today, purification of micr...

    journal_title：Nature medicine

    pub_type： 历史文章,杂志文章

    doi：10.1038/nm1209

    authors： Plotkin SA

    更新日期：2005-04-01 00:00:00

  • Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice.

    abstract：:The structure and function of blood vessels adapt to environmental changes such as physical development and exercise. This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow; however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel,...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1338

    authors： Yamamoto K,Sokabe T,Matsumoto T,Yoshimura K,Shibata M,Ohura N,Fukuda T,Sato T,Sekine K,Kato S,Isshiki M,Fujita T,Kobayashi M,Kawamura K,Masuda H,Kamiya A,Ando J

    更新日期：2006-01-01 00:00:00

  • Anti-cancer activity of targeted pro-apoptotic peptides.

    abstract：:We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. T...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/12469

    authors： Ellerby HM,Arap W,Ellerby LM,Kain R,Andrusiak R,Rio GD,Krajewski S,Lombardo CR,Rao R,Ruoslahti E,Bredesen DE,Pasqualini R

    更新日期：1999-09-01 00:00:00

  • Inhibition of gastric inhibitory polypeptide signaling prevents obesity.

    abstract：:Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with ins...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm727

    authors： Miyawaki K,Yamada Y,Ban N,Ihara Y,Tsukiyama K,Zhou H,Fujimoto S,Oku A,Tsuda K,Toyokuni S,Hiai H,Mizunoya W,Fushiki T,Holst JJ,Makino M,Tashita A,Kobara Y,Tsubamoto Y,Jinnouchi T,Jomori T,Seino Y

    更新日期：2002-07-01 00:00:00

  • Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.

    abstract：:The HIV-1-specific cytotoxic T lymphocyte (CTL) response is temporally associated with the decline in viremia during primary HIV-1 infection, but definitive evidence that it is of importance in virus containment has been lacking. Here we show that in a patient whose early CTL response was focused on a highly immunodom...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0297-205

    authors： Borrow P,Lewicki H,Wei X,Horwitz MS,Peffer N,Meyers H,Nelson JA,Gairin JE,Hahn BH,Oldstone MB,Shaw GM

    更新日期：1997-02-01 00:00:00

  • Cidea is an essential transcriptional coactivator regulating mammary gland secretion of milk lipids.

    abstract：:Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a resu...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2614

    authors： Wang W,Lv N,Zhang S,Shui G,Qian H,Zhang J,Chen Y,Ye J,Xie Y,Shen Y,Wenk MR,Li P

    更新日期：2012-01-15 00:00:00

  • A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity.

    abstract：:Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluores...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3182

    authors： Lodygin D,Odoardi F,Schläger C,Körner H,Kitz A,Nosov M,van den Brandt J,Reichardt HM,Haberl M,Flügel A

    更新日期：2013-06-01 00:00:00

  • Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.

    abstract：:Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to thera...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4407

    authors： Romero R,Sayin VI,Davidson SM,Bauer MR,Singh SX,LeBoeuf SE,Karakousi TR,Ellis DC,Bhutkar A,Sánchez-Rivera FJ,Subbaraj L,Martinez B,Bronson RT,Prigge JR,Schmidt EE,Thomas CJ,Goparaju C,Davies A,Dolgalev I,Heguy A,A

    更新日期：2017-11-01 00:00:00

  • Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients.

    abstract：:A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methioni...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0597-521

    authors： Silvestrini MC,Cardone F,Maras B,Pucci P,Barra D,Brunori M,Pocchiari M

    更新日期：1997-05-01 00:00:00

  • Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.

    abstract：:PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140...

    journal_title：Nature medicine

    pub_type： 杂志文章,随机对照试验

    doi：10.1038/s41591-020-0805-8

    authors： Chalabi M,Fanchi LF,Dijkstra KK,Van den Berg JG,Aalbers AG,Sikorska K,Lopez-Yurda M,Grootscholten C,Beets GL,Snaebjornsson P,Maas M,Mertz M,Veninga V,Bounova G,Broeks A,Beets-Tan RG,de Wijkerslooth TR,van Lent AU,Mars

    更新日期：2020-04-01 00:00:00