Abstract:
:Only humans and higher primates have high uric acid blood levels. Although high uric acid causes gout, it has been linked with human longevity because of its hypothetical antioxidant function. Recent studies reveal that p53 has significant roles in cellular metabolism. One example of this is an antioxidant function that potentially contributes to tumor suppression. Here, we reported a first beneficial link between p53 and uric acid. We identified the uric acid transporter SLC2A9 (also known as GLUT9) as a direct p53 target gene and a key downstream effector in the reduction of reactive oxygen species (ROS) through transporting uric acid as a source of antioxidant. Oxidative stress induced SLC2A9 expression in a p53-dependent manner, and inhibition of SLC2A9 by small interfering RNA (siRNA) or anti-gout drugs such as probenecid significantly increased ROS levels in an uric acid-dependent manner and greatly sensitized cancer cells to chemotherapeutic drugs. Conversely, expression of SLC2A9 reduced ROS and protected against DNA damage and cell death, suggesting its antioxidant function. The increased production of ROS because of p53 loss was rescued by SLC2A9 expression. Furthermore, decreased SLC2A9 expression was observed in several cancer types and was associated with a poorer prognosis. Our findings suggest that the p53-SLC2A9 pathway is a novel antioxidant mechanism that uses uric acid to maintain ROS homeostasis and prevent accumulation of ROS-associated damage that potentially contributes to cancer development.
journal_name
Oncogenejournal_title
Oncogeneauthors
Itahana Y,Han R,Barbier S,Lei Z,Rozen S,Itahana Kdoi
10.1038/onc.2014.119subject
Has Abstractpub_date
2015-04-02 00:00:00pages
1799-810issue
14eissn
0950-9232issn
1476-5594pii
onc2014119journal_volume
34pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 su...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206588
更新日期:2003-07-24 00:00:00
abstract::To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200818
更新日期:1997-01-23 00:00:00
abstract::Brahma (BRM) is a novel anticancer gene, which is frequently inactivated in a variety of tumor types. Unlike many anticancer genes, BRM is not mutated, but rather epigenetically silenced. In addition, histone deacetylase complex (HDAC) inhibitors are known to reverse BRM silencing, but they also inactivate it via acet...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.613
更新日期:2014-01-30 00:00:00
abstract::Transfection of primate tissue explants with a specific sub-fragment (p31) of EBV DNA results in epithelial (but no other) cells proliferating indefinitely (becoming 'immortalized') without evidence of a 'growth crisis'. Molecular evidence supports integration of viral information into the host chromosome, and an earl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205130
更新日期:2002-01-24 00:00:00
abstract::The signal transduction pathways, orchestrating the differentiation of hematopoietic stem and progenitor cells in response to cytokine stimulation, are strictly controlled by networks of feedback loops, highly selective protein interactions and finely tuned on/off switches. In hematological malignancies, the aberrant ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2012.435
更新日期:2013-06-27 00:00:00
abstract::Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209453
更新日期:2006-07-20 00:00:00
abstract::The maintenance of genome stability is essential for the cell as the integrity of genomic information guaranties reproduction of a whole organism. DNA damage occurring in response to different natural and nonnatural stimuli (errors in DNA replication, UV radiation, chemical agents, etc.) is normally detected by specia...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/s41388-019-0980-6
更新日期:2020-01-01 00:00:00
abstract::Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204137
更新日期:2001-02-08 00:00:00
abstract::High-risk papillomavirus type 18 (HPV18) is one of the less represented HPV types in low-grade lesions of the anogenital tract, whereas it occupies the second place in cervical cancer, where it can be found in 16% of the cases worldwide, after HPV16 present in 54% of them. These epidemiological data indicate that HPV1...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.246
更新日期:2010-09-09 00:00:00
abstract::The putative tumor suppressor CDKN1C is an imprinted gene at 11p15.5, a well-known imprinted region often deleted in tumors. The absence of somatic mutations and the frequent diminished expression in tumors would suggest that CDKN1C expression is regulated epigenetically. It has been, however, controversial whether th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207576
更新日期:2004-05-27 00:00:00
abstract::Scribble complex proteins maintain apicobasal polarity, regulate cell fate determination and function as tumour suppressors in epithelial tissue. Despite evidence that the function of Scribble is maintained in the lymphocyte lineage, we still understand little about its role as a tumour suppressor in haematological ma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.167
更新日期:2016-03-03 00:00:00
abstract::Induction of interstrand crosslinks (ICLs) in chromosomal DNA is considered a major reason for the antiproliferative effect of psoralen plus ultraviolet A (PUVA). It is unclear as to whether PUVA-induced cell cycle arrest is caused by ICLs mechanically stalling replication forks or by triggering cell cycle checkpoints...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206613
更新日期:2003-09-18 00:00:00
abstract::Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208828
更新日期:2005-10-13 00:00:00
abstract::We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201808
更新日期:1998-06-11 00:00:00
abstract::Pilocytic astrocytomas (PAs, WHO grade I) are the most common brain tumors in the pediatric and adolescent population, accounting for approximately one-fifth of central nervous system tumors. Because few consistent molecular alterations have been identified in PAs compared to higher grade gliomas, we performed array c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.110
更新日期:2008-08-07 00:00:00
abstract::Caspases are a family of cysteine proteases expressed as inactive zymogens in virtually all animal cells. These enzymes play a central role in most cell death pathways leading to apoptosis but growing evidences implicate caspases also in nonapoptotic functions. Several of these enzymes, activated in molecular platform...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208524
更新日期:2005-08-04 00:00:00
abstract::Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interaction...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0723-8
更新日期:2019-05-01 00:00:00
abstract::Genetic mutations of oncogenes often underlie deranged cell growth and altered differentiation pathways leading to malignant transformation of B-lymphocytes. However, addiction to oncogenes is not the only drive to lymphoid tumor pathogenesis. Dependence on non-oncogenes, which act by propelling basic mechanisms of ce...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.86
更新日期:2016-11-24 00:00:00
abstract::Small-cell lung cancer (SCLC) is an aggressive, rapidly metastasizing neoplasm. The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is constitutively secreted by marrow stromal cells and plays a key role for homing of hematopoietic cells to the marrow. Here, we report that tumor cells from patients with SCLC ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207097
更新日期:2003-11-06 00:00:00
abstract::Steroid receptor co-activator-3 (SRC-3/AIB1) is an oncogene that is amplified and overexpressed in many human cancers. However, the molecular mechanisms that regulate 'activated SRC-3 oncoprotein' turnover during tumorigenesis remain to be elucidated. Here, we report that speckle-type POZ protein (SPOP), a cullin 3 (C...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.151
更新日期:2011-10-20 00:00:00
abstract::The transcription factor E2F activates genes required for S phase, such as cyclin E and cyclin A. We show that, contrary to long term effects of E2F-1 overexpression, short ectopic overexpression of this transcription factor in logarithmically growing cells does neither affect the cell cycle distribution nor the cell ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201061
更新日期:1997-05-15 00:00:00
abstract::The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts. In contrast, MCP-1 transcription is absent in tumor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203643
更新日期:2000-07-06 00:00:00
abstract::Receptor tyrosine kinases (RTKs) control proliferation and differentiation through their ability to bind and/or phosphorylate intracellular substrates. The repertoire of substrates recruited by different RTK is largely overlapping. It is not clear, therefore, how a cell distinguishes among signals originating from dif...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-09-21 00:00:00
abstract::The role of intracellular Ca2+ pools in the regulation of growth factor signal transduction pathways and mitogenesis is not well understood. We have examined the roles of basal and transiently mobilized Ca2+ in the regulation of MAP kinases by EGF. To assess the influence of Ca2+ transients we utilized Plcg1-/- and Pl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203517
更新日期:2000-03-30 00:00:00
abstract::Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0374-1
更新日期:2018-10-01 00:00:00
abstract::Androgen receptor (AR) is overexpressed in the majority of castration-resistant prostate cancers (CRPCs). Our goal was to study the effect of AR overexpression on the chromatin binding of the receptor and to identify AR target genes that may be important in the emergence of CRPC. We have established two sublines of LN...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.401
更新日期:2012-04-26 00:00:00
abstract::Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0501-z
更新日期:2019-02-01 00:00:00
abstract::Activation of cellular transcriptional responses, mediated by hypoxia-inducible factor (HIF), is common in many types of cancer, and generally confers a poor prognosis. Known to induce many hundreds of protein-coding genes, HIF has also recently been shown to be a key regulator of the non-coding transcriptional respon...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.378
更新日期:2015-08-20 00:00:00
abstract::A large body of physiological evidence shows that either upregulation or downregulation of intracellular c-Myc activity has profound consequences on cell cycle progression. Recent work suggests that c-Myc may stimulate the activity of cyclin E/cyclin-dependent kinase 2 (Cdk2) complexes and antagonize the action of the...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1202749
更新日期:1999-05-13 00:00:00
abstract::Hepatitis B virus (HBV) infection is a major risk factor worldwide for the development of hepatocellular carcinoma (HCC). Integrated HBV DNA fragments, often highly rearranged, are frequently detected in HCC. In woodchuck, the viral enhancer plays a central role in hepatocarcinogenesis, but in humans the mechanism of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204879
更新日期:2001-10-18 00:00:00