Abstract:
:The expression of the cyclin-dependent kinase inhibitor p15INK4B in normal cells after induction with TGF-beta1, or following overexpression from an adenovirus-encoded cDNA, appears on an SDS-polyacrylamide gel as a doublet. Here, the underlying mechanism behind the synthesis of the two species has been studied. By expressing cDNAs truncated at their 5' end, we found that the synthesis of the more slowly migrating form, called p15.5INK4B, is dependent on a sequence upstream of the first AUG codon thought to initiate translation of p15INK4B. Two potential, in frame, alternative upstream initiation codons, ACG and GUG, were individually changed to GCA encoding alanine. Analysis by in vitro translation, or immunoblotting of lysates from transfected 293 cells, showed that translation of p15.5INK4B is initiated at the GUG located 13 codons upstream of the first AUG. When this AUG was mutated, p15INK4B was no longer made. Instead, a shorter form, initiated at an in frame AUG located seven codons downstream, was synthesized. Finally, when both these AUGs were mutated, only p15.5INK4B was generated. Both p15INK4B and p15.5INK4B bound to CDK4 and CDK6, inhibited DNA synthesis, and caused replicative senescence of a human glioma cell line. We thus conclude that p15INK4B and p15.5INK4B, encoded by the CDKN2B gene, are functionally indistinguishable as based on these assays.
journal_name
Oncogenejournal_title
Oncogeneauthors
Fuxe J,Raschperger E,Pettersson RFdoi
10.1038/sj.onc.1203496subject
Has Abstractpub_date
2000-03-23 00:00:00pages
1724-8issue
13eissn
0950-9232issn
1476-5594journal_volume
19pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Trichostatin A (TSA), a histone deacetylase inhibitor, strongly increases acetylation of the N-terminal tails of histone H3. Many studies have correlated the function of TSA with the hyperacetylation of histone. Although histone H3 is known to be phosphorylated, the effect of acetylation on phosphorylation is not know...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206507
更新日期:2003-08-14 00:00:00
abstract::Early Growth Response 1 (EGR1) is a stress response transcription factor with multiple tumour suppressor roles in breast tissue, whose expression is often lost in breast cancers. We have previously shown that the breast cancer oncogene TBX2 (T-BOX2) interacts with EGR1 to co-repress EGR1-target genes including the bre...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0853-z
更新日期:2019-08-01 00:00:00
abstract::Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204435
更新日期:2001-06-07 00:00:00
abstract::A wealth of cytogenetic data has demonstrated that numerous somatic genetic changes are involved in the pathogenesis of human lung cancer. Despite the complexity of the genomic changes observed in these neoplasms, recurrent chromosomal patterns have emerged. In this review, we summarize chromosomal alterations identif...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1205836
更新日期:2002-10-07 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::The osteogenic transcription factor, Runx2, is abnormally expressed in prostate cancer (PCa) and associated with metastatic disease. During bone development, Runx2 is activated by signals known to be hyperactive in PCa including the RAS/MAP kinase pathway, which phosphorylates Runx2 on multiple serine residues includi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.91
更新日期:2016-01-21 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::The p14ARF tumor suppressor is a key regulator of cellular proliferation, frequently inactivated in human cancer. The mechanisms that regulate alternative reading frame (ARF) turnover have been obscure for long time, being ARF a relatively stable protein. Recently, it has been described that its degradation depends, a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210313
更新日期:2007-08-02 00:00:00
abstract::Fos protein heterodimerizes through one surface of an alpha-helical domain called the leucine zipper. We have investigated the effect of destabilizing this domain by multiply substituting small residues of its non-interacting surface with glycine. Ternary complex formation between mutated Fos, Jun and DNA was determin...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-07-01 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 efficacy of anticancer therapy is limited by the development of drug resistance. While the role of p53 in the intrinsic sensitivity of human cancer cells to paclitaxel (PTX) remains controversial, its role in acquired paclitaxel resistance has never been addressed. In this study we examined the p53 status of three...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203642
更新日期:2000-06-22 00:00:00
abstract::CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have sug...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209247
更新日期:2006-04-06 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::FGFR1 (fibroblast growth factor receptor 1) regulates many key cellular responses including proliferation, migration and differentiation through activation of signaling pathways. Irregularities in FGFR1 signaling have been implicated in several pathological conditions, including human cancer. In order to discover nove...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.425
更新日期:2014-10-02 00:00:00
abstract::Activating mutations of K-ras are frequent in colon tumors and aberrant crypt foci, and may play important roles in colon carcinogenesis. Here, we investigated the effects of a K-ras codon 12 mutation on inducible nitric oxide synthase (iNOS) expression. When rat intestinal epithelial cells (IEC-6) were transfected wi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207051
更新日期:2003-10-23 00:00:00
abstract::We have characterized a novel chicken c-myb exon whose sequences are specifically expressed in thymic cells. In situ hybridization experiments indicate that this thymus-specific coding exon is localized on a small chromosome, distinct from the large acrocentric chromosome 3 on which we recently mapped the bulk of 15 e...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Tumor recurrence following treatment remains a major clinical challenge in oral cavity cancer. Cancer stem cells (CSCs) have been isolated from human oral cancers and been considered as the driving force of tumor recurrence and metastasis. However, it still remains unclear whether targeting CSCs in oral cancer is a cl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0800-z
更新日期:2019-07-01 00:00:00
abstract::Diffuse intrinsic pontine glioma (or DIPG) are pediatric high-grade gliomas associated with a dismal prognosis. They harbor specific substitution in histone H3 at position K27 that induces major epigenetic dysregulations. Most clinical trials failed so far to increase survival, and radiotherapy remains the most effici...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0884-5
更新日期:2019-09-01 00:00:00
abstract::High-grade serous carcinoma, accounts for up to 70% of all ovarian cases. Furin, a proprotein convertase, is highly expressed in high-grade serous carcinoma of ovarian cancer patients, and its expression is even higher in tumor omentum than in normal omentum, the preferred site of ovarian cancer metastasis. The proteo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1194-7
更新日期:2020-04-01 00:00:00
abstract::In order to assess the functional contribution of the human c-myc promoter region in the expression of the c-myc gene, transgenic mouse lines containing a bacterial lac Z gene encoding beta-galactosidase under the control of the human c-myc protooncogene promoter were generated. Transgenic mouse embryos heterozygous f...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-06-15 00:00:00
abstract::The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202409
更新日期:1999-02-04 00:00:00
abstract::We have previously demonstrated that daunorubicin (DNR) induces apoptosis in some leukemic myeloid cell lines. We investigated a potential protective role for Bcl-2 in apoptosis induced by DNR in two leukemic cell lines, one myeloid and one lymphoid, overexpressing the anti-apoptotic gene Bcl-2. Parental cells treated...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201023
更新日期:1997-04-17 00:00:00
abstract::Constitutive expression of the activated Rap1A protein inhibits differentiation of myogenic C2 cells whereas the inactivated Rap1A protein favours cell differentiation and induces late endocytic compartments clustering. Although the role of Rap1A in MAPK activation has been analysed in various cell types, the signalli...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203984
更新日期:2000-12-07 00:00:00
abstract::Adenovirus contains two nuclear oncogenes, the EIA and EIB genes, which cooperatively can transform cells through mechanisms that are not understood. The transcriptional activities of the E1A gene (transactivation and repression) are well studied. Using transient expression assays, we show here that the 19,000-Da E1B ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::BRCA1 mutation carriers have an increased susceptibility to breast and ovarian cancer. Excision of exon 11 of Brca1 in the mouse, using a conditional knockout (Cre-loxP) approach, results in mammary tumor formation after long latency. To characterize the genomic instability observed in these tumors, to establish a com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205636
更新日期:2002-08-01 00:00:00
abstract::The products of two cellular proto-oncogenes c-fos and c-jun form a heterodimeric complex that contribute to the DNA-binding activity referred to as AP-1 (activator protein-1). Two domains have been proposed to be required for heterodimer formation and protein-DNA complex formation. The leucine zipper domain mediated ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Using Southern blot analysis of DNA from mouse-hamster somatic cell hybrids, we have mapped Lmyc and Bmyc, two members of the myc family of genes, to mouse chromosomes 4 and 2, respectively. Furthermore, we have compared the regulation of Lmyc and Bmyc expression under different growth conditions and during in vitro d...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::In the present study, we have analysed the effects of transforming growth factor-beta (TGF-beta) signaling on the growth behavior of pancreatic carcinoma cells in vitro and on their tumorigenicity in vivo. Ectopic expression of dominant-negative mutants of the TGF-beta type II receptor or type I receptor/activin recep...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210272
更新日期:2007-07-19 00:00:00
abstract::Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interactio...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.67
更新日期:2015-03-05 00:00:00
abstract::Treating lung cancer cell lines using low-dose 5-aza-2'-deoxycytidine (DAC) caused an accumulation of procaspase-9 through mRNA upregulation, but the cells did not undergo apoptosis. However, when cells were treated with DAC and infected with a low dose of a recombinant wild-type p53 adenovirus vector (Ad-p53), a syne...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207381
更新日期:2004-09-02 00:00:00