Abstract:
:The E2F transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. We have previously shown that E2F3 plays a critical role in mediating the mitogen-induced activation of E2F-responsive genes and contributes to both the inappropriate proliferation and the p53-dependent apoptosis that arise in pRB-deficient embryos. Here we show that E2F3 also has a significant effect on the phenotype of tumor-prone Rb(+/-) mice. The absence of E2F3 results in a significant expansion in the life spans of these animals that correlates with a dramatic alteration in the tumor spectrum. E2F3 loss suppresses the development of the pituitary tumors that normally account for the death of Rb(+/-) mice. However, it also promotes the development of medullary thyroid carcinomas yielding metastases at a high frequency. This increased aggressiveness does not seem to result from any change in p53 levels or activity in these tumors. We show that, instead, E2F3 loss leads to an increase in the rate of tumor initiation. Finally, analysis of Rb(+/-); E2f3(+/-) mice shows that this tumor-suppressive function of E2F3 is dose dependent.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Ziebold U,Lee EY,Bronson RT,Lees JAdoi
10.1128/mcb.23.18.6542-6552.2003subject
Has Abstractpub_date
2003-09-01 00:00:00pages
6542-52issue
18eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::The Neurospora crassa arg-2 upstream open reading frame (uORF) plays a role in negative arginine-specific translational regulation. Primer extension inhibition analyses of arg-2 uORF-containing RNA translated in a cell-free system in which arginine-specific regulation was retained revealed "toeprints" corresponding to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.4904
更新日期:1997-09-01 00:00:00
abstract::A Dictyostelium discoideum cDNA encoding an alpha-type subunit of casein kinase II was isolated, and its cDNA was used to study developmental expression of casein kinase II during the Dictyostelium life cycle. The 1.3-kb cDNA insert contained an open reading frame of 337 amino acids (M(r) 39,900). The deduced amino ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.12.5711
更新日期:1992-12-01 00:00:00
abstract::The cardiac troponin C (cTnC) gene produces identical transcripts in slow-twitch skeletal muscle and in heart muscle (R. Gahlmann, R. Wade, P. Gunning, and L. Kedes, J. Mol. Biol. 201:379-391, 1988). A separate gene encodes the fast-twitch skeletal muscle troponin C and is not expressed in heart muscle. We have used t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.11.6752
更新日期:1993-11-01 00:00:00
abstract::CAP, a protein from Saccharomyces cerevisiae that copurifies with adenylyl cyclase, appears to be required for yeast cells to be fully responsive to RAS proteins. CAP also appears to be required for normal cell morphology and responsiveness to nutrient deprivation and excess. We describe here a molecular and phenotypi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1248
更新日期:1991-03-01 00:00:00
abstract::Nascent-polypeptide-associated complex and coactivator alpha (alpha NAC) is a protein shuttling between the nucleus and the cytoplasm. Upon phosphorylation at residue serine 43 by integrin-linked kinase, alpha NAC is translocated to the nuclei of osteoblasts, where it acts as an AP-1 coactivator to increase osteocalci...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00378-09
更新日期:2010-01-01 00:00:00
abstract::Rap1 (repressor activator protein 1) is a conserved multifunctional protein initially identified as a transcriptional regulator of ribosomal protein genes in Saccharomyces cerevisiae but subsequently shown to play diverse functions at multiple chromosomal loci, including telomeres. The function of Rap1 appears to be e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00986-09
更新日期:2010-03-01 00:00:00
abstract::GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein kinases. Substitution of a highly conserved lysine residue in the kinase domain abo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2820
更新日期:1990-06-01 00:00:00
abstract::Transcriptional activators interact with multisubunit coactivators that modify chromatin structure or recruit the general transcriptional machinery to their target genes. Budding yeast cells respond to amino acid starvation by inducing an activator of amino acid biosynthetic genes, Gcn4p. We conducted a comprehensive ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2800-2820.2003
更新日期:2003-04-01 00:00:00
abstract::The SNF3 gene of Saccharomyces cerevisiae encodes a high-affinity glucose transporter that is homologous to mammalian glucose transporters. Point mutations affecting the function of the transporter were recovered from the genomes of four snf3 mutants and characterized. Two of the mutations introduced a charged amino a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.1105
更新日期:1990-03-01 00:00:00
abstract::Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01185-12
更新日期:2013-01-01 00:00:00
abstract::The NuA4 histone acetyltransferase (HAT) multisubunit complex is responsible for acetylation of histone H4 and H2A N-terminal tails in yeast. Its catalytic component, Esa1, is essential for cell cycle progression, gene-specific regulation and has been implicated in DNA repair. Almost all NuA4 subunits have clear homol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.5.1884-1896.2004
更新日期:2004-03-01 00:00:00
abstract::The lck proto-oncogene encodes a lymphocyte-specific member of the src family of protein tyrosine kinases. Here we demonstrate that pp56lck is phosphorylated in vivo at a carboxy-terminal tyrosine residue (Tyr-505) analogous to Tyr-527 of pp60c-src. Substitution of phenylalanine for tyrosine at this position resulted ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.2.540
更新日期:1988-02-01 00:00:00
abstract::The 3' AU-rich region of human beta-1 interferon (hu-IFN beta) mRNA was found to act as a translational inhibitory element. The translational regulation of this 3' AU-rich sequence and the effect of its association with the poly(A) tail were studied in cell-free rabbit reticulocyte lysate. A poly(A)-rich hu-IFN beta m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3487
更新日期:1993-06-01 00:00:00
abstract::Deltex1, Deltex2, and Deltex4 form a family of related proteins that are the mammalian homologues of Drosophila Deltex, a known regulator of Notch signals. Deltex1 is highly induced by Notch signaling in thymocytes, and overexpression of Deltex1 in T-cell progenitors can block Notch signals, suggesting that Deltex1 ma...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00149-06
更新日期:2006-10-01 00:00:00
abstract::Extragenic suppressors of a new temperature-sensitive mutation (act1-4) in the actin gene of Saccharomyces cerevisiae were isolated in an attempt to identify genes whose products interact directly with actin. One suppressor with a cold-sensitive growth phenotype defined the new gene, SAC7, which was mapped, cloned, se...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.5.2308
更新日期:1990-05-01 00:00:00
abstract::Activating mutations in KEAP1-NRF2 are frequently found in tumors of the lung, esophagus, and liver, where they are associated with aggressive growth, resistance to cancer therapies, and low overall survival. Despite the fact that NRF2 is a validated driver of tumorigenesis and chemotherapeutic resistance, there are c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00377-20
更新日期:2020-10-26 00:00:00
abstract::The contribution of erythropoietin to the differentiation of the red blood cell lineage remains elusive, and the demonstration of a molecular link between erythropoietin and the transcription of genes associated with erythroid differentiation is lacking. In erythroid cells, expression of the tissue inhibitor of matrix...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.17.7412-7422.2005
更新日期:2005-09-01 00:00:00
abstract::Both cyclin D1 and the transcription factor C/EBPβ are required for mammary epithelial cell differentiation; however, the pathway in which they operate is uncertain. Previous analyses of the patterns of gene expression in human tumors suggested a connection between cyclin D1 overexpression and C/EBPβ, but whether this...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00039-14
更新日期:2014-08-01 00:00:00
abstract::The synthesis of 60S ribosomal subunits in Saccharomyces cerevisiae requires Tif6p, the yeast homologue of mammalian eukaryotic translation initiation factor 6 (eIF6). In the present work, we have isolated a protein kinase from rabbit reticulocyte lysates on the basis of its ability to phosphorylate recombinant human ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.17.6187-6199.2003
更新日期:2003-09-01 00:00:00
abstract::A region located at kbp -3.9 to -2.6 5' to the first hematopoietic exon of the GATA-1 gene is necessary to recapitulate gene expression in both the primitive and definitive erythroid lineages. In transfection analyses, this region activated reporter gene expression from an artificial promoter in a position- and orient...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.2.713-723.2000
更新日期:2000-01-01 00:00:00
abstract::The Drosophila melanogaster GAGA factor (encoded by the Trithorax-like [Trl] gene) is required for correct chromatin architecture at diverse chromosomal sites. The Trl gene encodes two alternatively spliced isoforms of the GAGA factor (GAGA-519 and GAGA-581) that are identical except for the length and sequence of the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.24.8565-8574.2001
更新日期:2001-12-01 00:00:00
abstract::To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UAS...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.2.442
更新日期:1989-02-01 00:00:00
abstract::The E1B 19-kilodalton protein (19K protein) is a potent apoptosis inhibitor and the adenovirus homolog of Bcl-2 (E. White, Genes Dev. 10:1-15, 1996). To obtain a better understanding of the biochemical mechanism by which the E1B 19K protein regulates apoptosis, proteins that interact with 19K have been identified; one...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.10.5857
更新日期:1996-10-01 00:00:00
abstract::Osteoclast differentiation factor (ODF)/receptor activator of NF-kappaB ligand is essential for inducing the differentiation of mature osteoclasts. We find that nuclear factor Y (NF-Y) binds to the CCAAT box on the ODF promoter and regulates its basal transcriptional activity. The CCAAT box on the ODF gene is required...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.1.512-522.2005
更新日期:2005-01-01 00:00:00
abstract::We have screened an adult rat cerebellar cDNA library in search of novel protein tyrosine-kinase (PTK) cDNAs. A cDNA for a putative PTK, trkB, was cloned, and its sequence indicates that it is likely to be derived from a gene for a ligand-regulated receptor closely related to the human trk oncogene. Northern (RNA) ana...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.1.143
更新日期:1991-01-01 00:00:00
abstract::The simian virus 40 72-base-pair repeats substituted for the polyomavirus enhancer, allowing replication and transcription in mouse 3T6 but not monkey CV-1 cells. A polyomavirus genome containing the entire simian virus 40 control region replicated at low levels in 3T6 and CV-1 cells; however, transcripts were detecte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.6.1534
更新日期:1985-06-01 00:00:00
abstract::All inbred strains of mice carry the Ren-1 structural gene, which encodes the renin-1 isozyme, the classical renin activity found in kidneys. In addition, some strains carry a second renin structural gene, Ren-2, which encodes the predominantly expressed submaxillary gland renin isozyme, renin-2. Ren-1 and Ren-2 exhib...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2321
更新日期:1984-11-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, null alleles of several DNA repair and recombination genes confer defects in recombination that grow more severe with decreasing sequence length, indicating that they are required for short-sequence recombination (SSR). RAD1 and RAD10, which encode the subunits of the str...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.15.5347-5356.2002
更新日期:2002-08-01 00:00:00
abstract::Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.480
更新日期:1988-01-01 00:00:00
abstract::Transcriptional silencing at the budding yeast silent mating type (HM) loci and telomeric DNA regions requires Sir2, a conserved NAD-dependent histone deacetylase, Sir3, Sir4, histones H3 and H4, and several DNA-binding proteins. Silencing at the yeast ribosomal DNA (rDNA) repeats requires a complex containing Sir2, N...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.12.4167-4180.2002
更新日期:2002-06-01 00:00:00