Abstract:
:The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3' cleavage step of the polyadenylation reaction, such as the tumor suppressor BARD1 and the 3' processing factor cleavage-stimulation factor 1 (CstF1). We found that p53 can coexist in complexes with CstF and BARD1 in extracts of UV-treated cells, suggesting a role for p53 in mRNA 3' cleavage following DNA damage. Consistent with this, we found that p53 inhibits 3' cleavage in vitro and that there is a reverse correlation between the levels of p53 expression and the levels of mRNA 3' cleavage under different cellular conditions. Supporting these results, a tumor-associated mutation in p53 not only decreases the interaction with BARD1 and CstF, but also decreases the UV-induced inhibition of 3' processing, all of which is restored by wild-type-p53 expression. We also found that p53 expression levels affect the polyadenylation levels of housekeeping genes, but not of p21 and c-fos genes, which are involved in the DNA damage response (DDR). Here, we identify a novel 3' RNA processing inhibitory function of p53, adding a new level of complexity to the DDR by linking RNA processing to the p53 network.
journal_name
Oncogenejournal_title
Oncogeneauthors
Nazeer FI,Devany E,Mohammed S,Fonseca D,Akukwe B,Taveras C,Kleiman FEdoi
10.1038/onc.2011.29subject
Has Abstractpub_date
2011-07-07 00:00:00pages
3073-83issue
27eissn
0950-9232issn
1476-5594pii
onc201129journal_volume
30pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Nuclear Foxc2 is a transcriptional regulator of mesenchymal transformation during developmental epithelial-mesenchymal transition (EMT) and has been associated with EMT in malignant epithelia. Our laboratory has shown that in normal epithelial cells Foxc2 is maintained in the cytoplasm where it promotes an epithelial ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.395
更新日期:2015-09-03 00:00:00
abstract::Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppre...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.253
更新日期:2017-11-16 00:00:00
abstract::Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+,HCO3--cotransporter NBCn1 (Slc4a7) to intracellular a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0353-6
更新日期:2018-10-01 00:00:00
abstract::In order to obtain insight into the parameters determining the subcellular localization of mutant and wild-type forms of p53, we analysed the subcellular distribution of p53 in four Balb/c mouse-derived cell lines ranging in their cellular phenotypes from normal (3T3), via minimal transformant (T3T3), to maximally tra...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.616
更新日期:2012-11-01 00:00:00
abstract::The mouse int6 gene is a frequent integration site of the mouse mammary tumor virus and INT6 silencing by RNA interference in HeLa cells causes an increased number of cells in the G2/M phases of the cell cycle, along with mitotic defects. In this report, we investigated the functional significance of the interaction b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210314
更新日期:2007-08-02 00:00:00
abstract::Activator protein one (AP1) (jun/fos) factors comprise a family of transcriptional regulators (c-jun, junB, junD, c-fos, FosB, Fra-1 and Fra-2) that are key controllers of epidermal keratinocyte survival and differentiation, and are important drivers of cancer development. Understanding the role of these factors in ep...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.315
更新日期:2010-11-04 00:00:00
abstract::Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a pla...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202341
更新日期:1999-01-21 00:00:00
abstract::Abnormalities in structure and expression of the proto-oncogene c-abl have been implicated in the genesis of chronic myelogenous leukemia (CML). We studied leukemic cell DNA from 42 CML patients for evidence of rearrangement and/or amplification of c-abl analogous to that described in the CML cell line K562. Using the...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1987-05-01 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::To gain better understanding of the molecular alterations responsible for the aggressive growth potential of epidermal growth factor receptor (EGFR)-positive breast cancers, we utilized an expression cloning strategy to seek gene products that mediate the EGF-independent growth of human breast cancer cells. A retrovir...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204537
更新日期:2001-07-05 00:00:00
abstract::The mechanisms of ras activation by mutations in residue 61 and in the NKXD guanine nucleotide-binding consensus sequence (ras residues 116-119) have been evaluated. Weakly transforming mutations that either reduce intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities (61P) or enhance guanine nucl...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::The v-myb oncogene of the avian myeloblastosis virus encodes a nuclear protein, p48v-myb, which binds to DNA in a sequence-specific manner. We have used wild type and mutant forms of this protein expressed in E. coli to study the protein and DNA determinants for sequence-specific DNA-binding. We have shown that only t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is generally accompanied by high mortality and low cure rate. CCAAT enhancer-binding proteins (CEBPs) are transcriptional regulators that play a key role in maintaining liver function. Altered expression of C/EBPα and C/EBPβ occurs in many tumours including HCC. saRNAs are small double-s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0665-6
更新日期:2019-05-01 00:00:00
abstract::Stimulation of the c-Kit receptor tyrosine kinase has a critical role in the development and migration of melanocytes, and oncogenic c-Kit mutants contribute to the progression of some melanomas. c-Kit signalling activates the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.562
更新日期:2014-01-09 00:00:00
abstract::Oncostatin M (OM) is a polypeptide cytokine that induces autocrine and paracrine effects on AIDS-Kaposi's sarcoma (KS) cells (Nair et al., Science, 255, 1430-1432, 1992; Miles et al., Science, 255, 1432-1434, 1992). The signalling pathways underlying this activation are largely unknown. We have found that OM binding t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The Epstein-Barr virus latency-associated membrane protein LMP2A has been shown to activate the survival kinase Akt in epithelial and B cells in a phosphoinositide 3-kinase-dependent fashion. In this study, we demonstrate that the signalling scaffold Shb associates through SH2 and PTB domain interactions with phosphor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210298
更新日期:2007-07-26 00:00:00
abstract::Prothymosin alpha (PT-alpha) is a nuclear protein involved in cell proliferation. Transcription of PT-alpha has been reported to be regulated by the c-myc gene in vitro. We identified PT-alpha as being overexpressed in a human colon cancer minus normal mucosa subtraction cDNA library. Northern blot (messenger RNA) ana...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::The transcription factor Cdx1 regulates intestine-specific gene expression and enterocyte differentiation. It has been hypothesized to play a role in regulating intestinal cell proliferation; however, the mechanism for this effect remains elusive. In a prior study, we demonstrated that Cdx1 expression reduced the prol...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206770
更新日期:2003-09-25 00:00:00
abstract::Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recogni...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203943
更新日期:2000-11-23 00:00:00
abstract::Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 sam...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201435
更新日期:1997-08-28 00:00:00
abstract::To achieve a better understanding of mechanisms that underlie hepatocarcinogenesis and to identify novel target molecules for diagnosis and therapy of hepatocellular carcinoma (HCC), we previously analysed gene-expression profiles of 20 HCC tissues on a cDNA microarray. Among the genes upregulated in the tumor tissues...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209517
更新日期:2006-08-17 00:00:00
abstract::Smad4 is a critical component in transforming growth factor beta (TGF-beta) signaling and frequently mutated in pancreatic and colorectal cancers. Smad4 has two important functional domains, MH1 and MH2, that are involved in different biological processes. The MH1 domain comprises a DNA binding domain and the MH2 doma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207219
更新日期:2004-02-05 00:00:00
abstract::p21(Waf1/Cip1) is a p53 transcription target implicated in both major functions of the tumor suppressor--cell cycle arrest and apoptosis. It is a potent inhibitor of the key cyclin-dependent kinases (CDK1-4), and has been thought to be the main mediator of p53-dependent G1 and G2 arrest. However, an increasing body of...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.413
更新日期:2011-01-20 00:00:00
abstract::The function of the class III histone deacetylase, Sir2, in promoting lifespan extension is well established in small model organisms. By analogy, SirT1, the mammalian orthologue of Sir2, is a candidate gene to slow down aging and forestall the onset of age-associated diseases. We have used SirT1-null mice to study th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.147
更新日期:2009-08-13 00:00:00
abstract::Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207063
更新日期:2003-11-20 00:00:00
abstract::Ufo/Axl belongs to a new family of receptor tyrosine kinases with an extracellular structure similar to that of neural cell adhesion molecules. In order to elucidate intracellular signaling, the cytoplasmic moiety of Ufo/Axl was used to screen an expression library according to the CORT (cloning of receptor targets) m...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201123
更新日期:1997-06-05 00:00:00
abstract::Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of beta-catenin. We here demonstrate that a functional crosstalk between Met and beta-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209859
更新日期:2007-02-15 00:00:00
abstract::Interleukin-6 (IL-6) is a cytokine that regulates the proliferation of some tumor cells including multiple myeloma (MM). Ectopic expression of fibroblast growth factor receptor 3 (FGFR 3) associated with the chromosomal translocation, t(4;14)(p16.3;q32), is frequently found in MM, and therefore, has been implicated in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208782
更新日期:2005-09-15 00:00:00
abstract::DNA double-stranded breaks (DSBs) elicit a checkpoint response that causes a delay in cell cycle progression. Early in the checkpoint response, histone H2AX is phosphorylated in the chromatin region flanking the DSB by ATM/ATR and DNA-PK kinases. The resulting foci of phosphorylated H2AX (gamma-H2AX) serve as a platfo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.501
更新日期:2010-04-15 00:00:00