Abstract:
:The p53 protein is a multifunctional transcription factor which orchestrates cellular responses to DNA damage, so helping to conserve genomic stability. It may also regulate genes involved in intercellular signalling, such as thrombospondin, a negative regulator of angiogenesis and metastatic spread. Activation of p53 target genes requires sequence-specific DNA binding, a function which maps to the central core of the protein. Missense point mutations within this domain inactivate p53 tumour suppressor function and involve either (i) DNA contact residues, or (ii) residues important for conformational structure. Using in vitro techniques we have analysed seven DNA contact mutants and 17 structural mutants known to occur in cancer. We show that DNA contact mutants can be carried into specific DNA interaction when co-expressed with wild type protein. For structural mutants, 9/17 retained DNA binding capacity and, with one exception, DNA binding correlated with conformational flexibility of the mutant protein. The exception was Asp281, which appeared essential for DNA interaction, probably due to its ability to form salt bridges with DNA contact residues Arg273 and Arg280. We suggest that different classes of p53 mutant may prove amenable to different strategies for restoration of wild type tumour suppressor function as means of anti-cancer therapy.
journal_name
Oncogenejournal_title
Oncogeneauthors
Rolley N,Butcher S,Milner Jsubject
Has Abstractpub_date
1995-08-17 00:00:00pages
763-70issue
4eissn
0950-9232issn
1476-5594journal_volume
11pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-kappaB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208008
更新日期:2004-10-28 00:00:00
abstract::Pax3 is an evolutionarily conserved transcription factor that plays a major role in a variety of developmental processes. Mutations in Pax3 lead to severe malformations as seen in human Waardenburg syndrome and in the Splotch mutant mice. The transcriptional activity of Pax3 was recently shown to be repressed by Daxx ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204063
更新日期:2001-01-04 00:00:00
abstract::The E2F1 transcription factor, which is deregulated in most human cancers by mutations in the p16-cyclin D-Rb pathway, has both oncogenic and tumor-suppressive properties. This is dramatically illustrated by the phenotype of an E2F1 transgenic mouse model that spontaneously develops tumors in the skin and other epithe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209120
更新日期:2006-02-09 00:00:00
abstract::The chromatin organizer SATB1 has been implicated in the development and progression of multiple cancers including breast and colorectal cancers. However, the regulation and role of SATB1 in colorectal cancers is poorly understood. Here, we demonstrate that expression of SATB1 is induced upon hyperactivation of Wnt/β-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.232
更新日期:2016-03-31 00:00:00
abstract::Jun : Fos and Jun : ATF complexes represent two classes of AP-1 dimers that (1) preferentially bind to either heptameric or octameric AP-1 binding sites, and (2) are differently regulated by cellular signaling pathways and oncogene products. To discriminate between the functions of Jun : Fos, Jun : ATF and Jun : Jun, ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1204239
更新日期:2001-04-30 00:00:00
abstract::There are at least three distinct MAP kinase signaling modules in mammalian cells, distinguished by the family of kinases (Erk, SAPK/JNK, or p38) that is ultimately activated. Many input signals activate multiple MAP kinase cascades, and the mechanisms that control the specificity of signal output are not well underst...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203057
更新日期:1999-11-18 00:00:00
abstract::The release of cytochrome c from the intermembrane space of mitochondria into the cytosol is one of the critical events in apoptotic cell death. In the present study, it is shown that release of cytochrome c and apoptosis induced by tumor necrosis factor alpha (TNF) in HeLa cells can be inhibited by (i) overexpression...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206053
更新日期:2002-11-21 00:00:00
abstract::Procollagen lysyl hydroxylase 1 (PLOD1) is highly expressed in malignant tumors such as esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer. Bioinformatics analysis revealed that PLOD1 is associated with the progression of GBM, particularly the most malignant mesenchymal subtype (MES). Moreover, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01635-y
更新日期:2021-01-08 00:00:00
abstract::We have characterized a chromosomal translocation in a cell line (SU-DUL5) established from a patient with lymphoblastic lymphoma in which the c-myc gene on chromosome 8 was juxtaposed to a t(14;18). Cytogenetic analysis of this cell line showed 14q+, 18q-, and 8p+q+ marker chromosomes in the absence of t(14;18). Geno...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-08-15 00:00:00
abstract::Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.91
更新日期:2009-07-02 00:00:00
abstract::The von Hippel-Lindau tumor suppressor pVHL regulates the stability of hypoxia-inducible factors (HIF)-1 and -2, oxygen-sensitive basic helix-loop-helix transcription factors, which mediate the hypoxic induction of angiogenic growth factors such as vascular endothelial growth factor. Loss of pVHL function results in c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.160
更新日期:2008-09-11 00:00:00
abstract::The Kruppel-like transcription factor KLF6 is a novel tumor-suppressor gene mutated in a significant fraction of human prostate cancer. It is localized to human chromosome 10p14-15, a region that displays frequent loss of heterozygosity in glioblastoma multiforme (GBM). Indeed, mutations of the KLF6 gene have recently...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207662
更新日期:2004-06-24 00:00:00
abstract::The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201939
更新日期:1998-07-16 00:00:00
abstract::Making decisions between self-renewal and differentiation is a central ability of stem cells. Elucidation of molecular networks governing this decision is therefore of prime importance. A model of choice to explore this question is represented by chicken erythroid progenitors, in which self-renewal versus differentiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207049
更新日期:2003-12-18 00:00:00
abstract::Oncogene-induced senescence (OIS) is an intrinsic tumor suppression mechanism that requires the p53 and RB pathways and post-translational activation of C/EBPβ through the RAS-ERK cascade. We previously reported that in transformed/proliferating cells, C/EBPβ activation is inhibited by G/U-rich elements (GREs) in its ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0190-7
更新日期:2018-06-01 00:00:00
abstract::Delta(9)-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers,...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210641
更新日期:2008-01-10 00:00:00
abstract::Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistan...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1245-0
更新日期:2020-04-01 00:00:00
abstract::Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor that is activated by trypsin-like proteinases. PAR2 is detected in breast tumor specimens; however, it is not clear how PAR2 level in breast cancer cell/tissues compares with normal cell/tissues. Here, we show the elevation of PAR2 protein level in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.163
更新日期:2009-08-27 00:00:00
abstract::Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer. IL-17 pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.240
更新日期:2017-02-02 00:00:00
abstract::While studying Bim, a BH3-only proapoptotic protein, we identified an approximately 36 kDa protein, which was abundantly expressed in all five strains of primary normal human prostate (NHP) epithelial cells but significantly reduced or lost in seven prostate cancer cell lines. The approximately 36 kDa protein was subs...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206196
更新日期:2003-03-13 00:00:00
abstract::Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. This phenomenon, termed the 'bystander response', has been shown to occur both in vi...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1206961
更新日期:2003-10-13 00:00:00
abstract::DDB2, a gene mutated in XPE patients, is involved in global genomic repair especially the repair of cyclobutane pyrimidine dimers (CPDs), and is regulated by p53 in human cells. We show that DDB2 is expressed in mouse tissues and demonstrate, using primary mouse epithelial cells, that mouse DDB2 is regulated by E2F tr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210151
更新日期:2007-05-24 00:00:00
abstract::Dlk/ZIP kinase is a newly discovered serine/threonine kinase which, due to its homology to DAP kinase, was named DAP like kinase, Dlk. This kinase is tightly associated with nuclear structures, it undergoes extensive autophosphorylation and phosphorylates myosin light chain and core histones H3, H2A and H4 in vitro. M...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203170
更新日期:1999-12-02 00:00:00
abstract::Over 70% of human breast cancers are estrogen receptor-positive (ER+), most of which express MYB. In these and other cell types, the MYB transcription factor regulates the expression of many genes involved in cell proliferation, differentiation, tumorigenesis, and apoptosis. So far, no clear link has been established ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0789-3
更新日期:2019-06-01 00:00:00
abstract::The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207773
更新日期:2004-07-29 00:00:00
abstract::Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that protects cells from the negative consequences of endoplasmic reticulum (ER) stress. In this study, we have used small inter...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.191
更新日期:2010-08-05 00:00:00
abstract::Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and thei...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-05 00:00:00
abstract::The biological outcome of TMPRSS2:ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2:ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2:ERG-positive PC cell line. This reveals that ERG re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.308
更新日期:2015-07-01 00:00:00
abstract::Previous studies have shown that increased expression of oncogenes from the myc-family can down-regulate the level of MHC class I antigens in tumor cells. This has suggested a mechanism by which amplification/overexpression of myc-genes may contribute to the malignancy development of certain tumors. Earlier published ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00