Abstract
We previously reported the identification of DP-1 isoforms (alpha and beta), which are structurally C-terminus-deleted ones, and revealed the low-level expression of these isoforms. It is known that wild-type DP-1 is degraded by the ubiquitin-proteasome system, but few details are known about the do...
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PMID: 20513349
PDF is available here.
Abstract
We report here on the molecular basis of this activity. Cell cycle suppression by Cdk5 requires its binding to the p35 activator protein. The related p39 and p25 proteins cannot serve as substitutes. Unexpectedly, Cdk5 enzymatic activity is not required to perform this function. Rather, the link to...
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PMID: 20392944
PDF is available here.
Abstract
We conclude that 13q34 amplification may be of relevance in tumor progression of basal-like breast cancers by inducing overexpression of CUL4A and TFDP1, which are both important in cell cycle regulation. Alternatively, as these genes were also overexpressed in non-basal-like tumor samples, they cou...
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PMID: 19995430
PDF is available here.
Abstract
We used yeast two-hybrid screening to find proteins interacting with human SOCS-3. We identified the transcriptional factor DP-1 as a SOCS-3-interacting protein involved in regulation of the cell cycle. Immunoprecipitation-Western blot assay showed that this interaction between these endogenous prot...
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PMID: 18687693
PDF is available here.
Abstract
We present a quantitative analysis of nuclear membrane assembly in mammalian cells using time-lapse microscopy. From the initial recruitment of ER tubules to chromatin, the formation of a membrane-enclosed, transport-competent nucleus occurs within approximately 12 min. Overexpression of the ER tubu...
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PMID: 18779370
PDF is available here.
Abstract
Met-Arg-Trp (MRW) has been isolated as an inhibitor for angiotensin I-converting enzyme (ACE) from a pepsin-pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco) (IC(50)=0.6 microM). It has been reported that hypotensive activity of ACE-inhibitory peptides derived from f...
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PMID: 18180074
PDF is available here.
Abstract
The E2F family of transcription factors regulate the expression of many growth-related genes in a cell cycle-dependent manner. These transcription factors can activate or, in conjunction with an Rb-related protein, repress transcription. E2F transcriptional activity is regulated at several different...
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PMID: 17894419
PDF is available here.
Abstract
We have previously shown that overexpression of a dominant negative form of the cJun proto-oncogene, a cJun dominant negative mutant (Tam67), blocks AP-1 transcriptional activity, induces a G(1) cell cycle block and inhibits breast cancer cell growth in vitro and in vivo. We found that AP-1 blockade...
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PMID: 17637753
PDF is available here.
Abstract
By dimerizing with E2F proteins, TFDP has profound influence on cellular E2F activities. While TFDP1 and 2 enhance the DNA binding and the transcriptional activity of E2F, the newly identified member of the DP family, TFDP3 primarily functions as a negative regulator. To further characterize the inh...
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PMID: 17632080
PDF is available here.
Huan H Qiao,
Luisa L Di Stefano,
Chan C Tian,
Yun-Yan YY Li,
Yan-Hui YH Yin,
Xiao-Ping XP Qian,
Xue-Wen XW Pang,
Yan Y Li,
Michael Allen MA McNutt,
Kristian K Helin,
Yu Y Zhang and
Wei-Feng WF Chen
Abstract
We report the identification of a new member of the DP family, human TFDP3. Despite the high degree of sequence similarity, TFDP3 is apparently distinct from TFDP1 in function. Although TFDP3 retained the capacity to bind to E2F proteins, the resulting heterodimers failed to interact with the E2F co...
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PMID: 17062573
PDF is available here.
Abstract
We identified suppressors of an mat3 null allele that had recessive mutations in DP1 or dominant mutations in E2F1, loci encoding homologs of a heterodimeric transcription factor that is targeted by RB-related proteins. Significantly, we determined that the dp1 and e2f1 phenotypes were caused by def...
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PMID: 17040130
PDF is available here.
Abstract
We show that, upon growth stimulation, the same region is subject to variations of H3-R17 and H3-R26 methylation that correlate with the recruitment of coactivator-associated arginine methyltransferase 1 (CARM1) onto the CCNE1 and DHFR promoters. Accordingly, CARM1-deficient cells lack these modific...
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PMID: 16938873
PDF is available here.
Abstract
We show here that E2F4 specifically and directly interacts with HCF-1. Mutational analysis showed E2F4 independently targets the kelch domain and the basic domain (residues 450-902) of HCF-1, both of which are required for normal cell-cycle progression via separate determinants. The HBM-containing d...
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PMID: 16633736
PDF is available here.
Abstract
We show that E2Fs (E2 promoter-binding factors) regulate the expression of ASK-1 (apoptosis signal-regulating kinase 1), which encodes a mitogen-activated protein kinase kinase kinase, also known as MAP3K5. Its mRNA expression is cell-cycle-regulated in human T98G cells released from serum starvatio...
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PMID: 16512785
PDF is available here.
Abstract
We review the molecular mechanisms that regulate cell division and endoreduplication and we discuss our understanding, albeit very limited, on how the cell cycle is integrated with plant development....
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PMID: 17094738
PDF is available here.
Abstract
We demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members. The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate that phosp...
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PMID: 16360038
PDF is available here.
Abstract
We have investigated the interaction between the tumor suppressor ARF and DP1, the DNA binding partner of the E2F family of factors (E2Fs). We show that ARF directly binds to DP1. Interestingly, binding of ARF to DP1 results in an inhibition of the interaction between DP1 and E2F1. Moreover, ARF reg...
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PMID: 16135794
PDF is available here.
Abstract
We identified two novel DP-1 isoforms (DP-1alpha and DP-1beta) and characterized their structure and function. DP-1alpha is composed of 278 amino acids and lacks a portion of the C-terminal heterodimerization domain, whereas DP-1beta is composed of 357 amino acids with a frameshift that causes trunc...
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PMID: 15863509
PDF is available here.
Abstract
We provide evidence that depletion of DP by RNA interference, but not overexpression of dominant-negative form of E2F, efficiently reduces endogenous E2F/DP activity in human primary cells. Reduction of total E2F/DP activity results in a dramatic decrease in expression of many E2F target genes and c...
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PMID: 15716376
PDF is available here.
Abstract
We assayed preimplantation mouse embryos for the acquisition of expression of mRNA, protein, and phospho-protein for max, Rb, and DP-1, and for the proliferation-promoting phospho-protein forms of mycC (thr58/ser62) and Rb (ser795). The key findings are that: (1) DP-1 protein was present in the nucl...
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PMID: 15642350
PDF is available here.
Abstract
We searched for novel E2F6-binding proteins using a yeast two-hybrid screen and identified the PcG protein, EPC1. We showed that, both in vitro and in vivo, E2F6, DP1, and EPC1 form a stable core complex with repressive activity. Furthermore, we identified the proliferation-specific PcG, EZH2, as an...
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PMID: 15536069
PDF is available here.
Abstract
We inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysi...
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PMID: 15448153
PDF is available here.
Abstract
We have recently demonstrated that loss of Dp1 results in embryonic lethality by embryonic day 12.5 (E12.5) due to the failure of extraembryonic lineages to develop and replicate DNA properly. To bypass this placental requirement and search for roles of Dp1 in the embryo proper, we generated Dp1-def...
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PMID: 15282318
PDF is available here.
Abstract
We describe a system designed to express biotinylated proteins in mammalian cells in vivo and its application to the study of protein-DNA interactions in vivo by chromatin immunoprecipitation (ChIP). The system is based on coexpression of the target protein fused to a short biotin acceptor domain to...
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PMID: 14715286
PDF is available here.
Abstract
A conditional mouse model of time-dependent dysplasia reversal demonstrated that reversal and differentiation of dysplastic salivary gland tissue at the 4-month reversible stage was characterized by the appearance of a phosphorylated slower mobility form of Differentiation Related Transcription Fact...
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PMID: 14633688
PDF is available here.
Abstract
We demonstrate that flavopiridol treatment during S phase traversal results in persistent expression of E2F-1. The phosphorylation of E2F-1 is markedly diminished, whereas that of the retinoblastoma protein is minimally affected, so that E2F-1/DP-1 heterodimers remain bound to DNA. In addition, mani...
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PMID: 14612540
PDF is available here.
Abstract
DP1 and DP2 function as binding partners for E2F transcription factors. The association of DP with E2F directly enhances both the DNA binding affinity and the transactivation function of the heterodimer. Target genes include those involved in DNA synthesis, cell cycle and apoptosis. E2F/DP activity i...
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PMID: 12975577
PDF is available here.
Kwan-Kyu KK Park,
Jong J Deok Ahn,
In-Kyu IK Lee,
Junji J Magae,
Nicholas H NH Heintz,
Jong-Young JY Kwak,
Young-Choon YC Lee,
Young-Su YS Cho,
Hyun-Chul HC Kim,
Young-Mi YM Chae,
Young Y Ho Kim,
Cheorl-Ho CH Kim and
Young-Chae YC Chang
Abstract
We investigated the role of E2F1 and E2F4 expression, with or without co-expression of DP1 or DP2, on cell proliferation in transiently transfected primary rat MCs. In transfected cells, cell proliferation induced by over-expression of E2F was significantly enhanced by co-expression of DP proteins....
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PMID: 12927774
PDF is available here.
Abstract
Cyclin-dependent kinase 2 (CDK2) regulates diverse aspects of the mammalian cell cycle. Most cancer cells contain mutations in the pathways that control CDK2, and CDK2 activity has received much attention as a target for cancer therapy. However, a recent report demonstrating that some cancer cells c...
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PMID: 12888290
PDF is available here.
Abstract
We report that loss of Dp1 leads to death in utero because of the failure of extra-embryonic development. Loss of Dp1 compromises the trophectoderm-derived tissues - specifically, the expansion of the ectoplacental cone and chorion, and endoreduplication in trophoblast giant cells. Inactivation of p...
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PMID: 12588846
PDF is available here.
Abstract
We show here that E2F-1 elevates ATM promoter activity and induces an increase in ATM mRNA and protein levels. This is accompanied by an E2F-induced increase in p53 phosphorylation. Expression of the E7 protein of HPV16, which dissociates RB/E2F complexes, also induces the elevation of ATM levels an...
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PMID: 12527885
PDF is available here.
Abstract
We determined expression levels of TFDP1 and E2F1 in 41 primary HCCs by means of quantitative real-time reverse transcription-polymerase chain reactions, and looked for relationships between those data and various clinicopathological parameters. To assess transactivating activity of E2F1/DP-1, we al...
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PMID: 14618416
PDF is available here.
Abstract
DP-1 is a G1 cell cycle-related protein that forms heterodimers with E2F, a family of transcriptional factors regulating the expression of genes important for G1 to S progression. Although the exact role of DP-1 is not well understood, it has been shown to stabilize DNA binding of E2F proteins. By i...
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PMID: 12607600
PDF is available here.
Abstract
We investigated whether DP1 is also regulated by ARF. Here we show that DP1 associates with ARF. Coexpression of ARF relocalizes DP1 from the cytoplasm to the nucleolus, suggesting that DP1 is also a target of the ARF regulatory pathways. Surprisingly, however, the E2F1/DP1 complex is refractory to...
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PMID: 12446760
PDF is available here.
Abstract
We suggest that Yop1p/HVA22 regulates vesicular traffic in stressed cells either to facilitate membrane turnover, or to decrease unnecessary secretion....
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PMID: 12427979
PDF is available here.
Abstract
Apoptotic cell death is an important mode of cell loss contributing to heart dysfunction. To analyze the importance of the E2F-dependent regulation of gene transcription in cardiomyocyte apoptosis, the function of cell cycle factors impinging on the retinoblastoma protein (pRb)/E2F pathway was inves...
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PMID: 12411392
PDF is available here.
Yu Y Wang,
Ke-Jun KJ Han,
Xue-Wen XW Pang,
Hilary A HA Vaughan,
Wei W Qu,
Xue-Yuan XY Dong,
Ji-Run JR Peng,
Hai-Tao HT Zhao,
Jing-An JA Rui,
Xi-Sheng XS Leng,
Jonathan J Cebon,
Antony W AW Burgess and
Wei-Feng WF Chen
Abstract
We identified 55 independent cDNA sequences potentially encoding HCC tumor Ags. Of these genes, 15 are novel. Two such proteins, HCA587 and HCA661, were predominantly detected in testis, but not in other normal tissues, except for a weak expression in normal pancreas. In addition to HCC, these two A...
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PMID: 12097419
PDF is available here.
Abstract
We defined how, in the same context, Smad3 can also mediate transcriptional repression of the growth-promoting gene c-myc. A complex containing Smad3, the transcription factors E2F4/5 and DP1, and the corepressor p107 preexists in the cytoplasm. In response to TGFbeta, this complex moves into the nu...
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PMID: 12150994
PDF is available here.
Abstract
We carried out molecular cytogenetic characterization of 11 cell lines derived from hepatocellular carcinomas (HCCs) and 51 primary HCCs. Comparative genomic hybridization (CGH) revealed frequent amplification at 13q34, where we had detected amplification in several other types of tumor, including e...
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PMID: 12029633
PDF is available here.
Abstract
We evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrai...
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PMID: 12029619
PDF is available here.
Abstract
Although in the normal lens there do not appear to be unique roles for E2F1 that cannot be fulfilled by other E2F family members, in the absence of functional pRB proteins, E2F1 is specifically responsible for the increased expression of E2F3a and p19ARF. These findings suggest that E2F1 may be the...
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PMID: 11980867
PDF is available here.
Abstract
We employed a dominant-negative DP-1, which suppresses both E2F-dependent transactivation and the formation of active transcriptional repressors. Ectopic expression of the dominant negative DP-1 in the IL-3-dependent BaF3 lymphoid cells gave rise to an inhibition of cell proliferation, which was con...
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PMID: 11886176
PDF is available here.
Abstract
We have designed a novel peptide, DP1, which is able to mediate significant induction of apoptosis in solid tumors by local injection. This peptide, comprised of a protein transduction domain (PTD), PTD-5, fused to an antimicrobial peptide, (KLAKLAK)2, was able to trigger rapid apoptosis in a variet...
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PMID: 11691780
PDF is available here.
Abstract
We sought to identify additional C/EBPalpha target genes essential for myeloid cell development. To identify such genes, we used both representational difference analysis and oligonucleotide array analysis with RNA derived from a C/EBPalpha-inducible myeloid cell line. From each of these independent...
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PMID: 11340171
PDF is available here.
Abstract
We have found that pRb causes a posttranscriptional accumulation of the cyclin-dependent kinase inhibitor p27(KIP1) that is accompanied by an increase in p27(KIP1) specifically bound to cyclin E and a concomitant decrease in cyclin E-associated kinase activity. In contrast, pRb-related proteins p107...
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PMID: 11340156
PDF is available here.
Abstract
We generated transgenic mouse lines expressing DP1 under the control of a keratin 5 (K5) promoter. Overexpression of DP1 in basal layer keratinocytes caused mild hyperplasia and hyperproliferation of the epidermis but did not result in increased apoptosis or spontaneous tumor development. Coexpressi...
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PMID: 11429786
PDF is available here.
Abstract
The balance between cell differentiation and proliferation is regulated at the transcriptional level. In the cell cycle, the transition from G1 to S phase (G1/S transition) is of paramount importance in this regard. Indeed, it is only before this point that cells can be oriented toward the different...
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PMID: 11420729
PDF is available here.
Abstract
We undertook the present study to examine alterations affecting the RB pathway in the G1 checkpoint and to determine their potential clinical significance in children affected with nonfamilial retinoblastoma. Using immunohistochemistry, patterns of expression of pRB, p16/INK4A, and E2F1 were analyze...
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PMID: 11381373
PDF is available here.
Abstract
We examine the linkage between cell adhesion and IGF-1 expression. While IGF-1 is able to maintain Akt activity and phosphorylation of proapoptotic proteins in cells that have lost matrix contact, Akt is not able to phosphorylate and inactivate another of its substrates, glycogen synthase kinase 3be...
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PMID: 11313458
PDF is available here.
Abstract
We report the isolation of TRIP-Br1, a transcriptional regulator that interacts with the PHD-bromodomain of co-repressors of Krüppel-associated box (KRAB)-mediated repression, KRIP-1(TIF1beta) and TIF1alpha, as well as the co-activator/adaptor p300/CBP. TRIP-Br1 and the related protein TRIP-Br2 pos...
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PMID: 11331592
PDF is available here.
Abstract
We report that Rb is a binding target for Ebp1. Ebp1 was localized to both the nucleus and the cytoplasm of logarithmically growing AU565 breast cancer cells and HeLa cells as determined by confocal immunofluorescent microscopy. Ebp1 was present in Rb immunoprecipitates derived from AU565 breast can...
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PMID: 11268000
PDF is available here.
Abstract
We studied the influence of a wide concentration range of the synthetic androgen R1881 on several cell cycle- and differentiation-related parameters. Low concentrations (0.1 nM), known to promote LNCaP cell proliferation, induce an increase of Retinoblastoma protein phosphorylation, accompanied by a...
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PMID: 11322773
PDF is available here.
Abstract
This report characterizes the influence of a pharmacological concentration of estradiol on growth arrest and cell death in MCF-7 breast tumor cells, with a focus on elements of the Rb-E2F cell-cycle regulatory pathway. Continuous exposure of MCF-7 breast tumor cells to 100 microM estradiol produces...
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PMID: 11368161
PDF is available here.
Abstract
We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in human T-cell line Kit 225 cells. To elucidate molecular mechanism of Tax-induced cell cycle progression, we systematically examined the effects of Tax on biochemical events associated with cell cy...
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PMID: 11360190
PDF is available here.
Abstract
These results suggest a broader role for p19ARF as a tumor suppressor, in which targeting of certain E2F species may cooperate with stimulation of the p53 pathway to counteract oncogenic growth signals....
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PMID: 11274364
PDF is available here.
Abstract
INTRODUCTION: Comprehension of cell cycle regulation mechanisms has progressed very quickly these past few years and regulators of the cell cycle have gained widespread importance in cancer. This review first summarizes major advances in the understanding of the control of cell cycle mechanisms. Exam...
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PMID: 11355576
PDF is available here.
Abstract
The E2F decoy oligonucleotide, but not scrambled oligonucleotide or vehicle alone, inhibited proliferating cell nuclear antigen expression and smooth muscle cell proliferation. Furthermore, this manipulation of cell-cycle gene expression yielded an inhibition of neointimal hyperplasia and atheroscle...
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PMID: 11279413
PDF is available here.