34 results match your criteria e1a terminally

Inhibition of androgen receptor transactivation function by adenovirus type 12 E1A undermines prostate cancer cell survival.

Prostate 2018 11 15;78(15):1140-1156. Epub 2018 Jul 15.

Department of Anatomy and Cell Biology, UF Health Cancer Center and UF Genetics Institute, University of Florida College of Medicine, Gainesville, Florida.

Background: Mutations or truncation of the ligand-binding domain (LBD) of androgen receptor (AR) underlie treatment resistance for prostate cancer (PCa). Thus, targeting the AR N-terminal domain (NTD) could overcome such resistance.

Methods: Luciferase reporter assays after transient transfection of various DNA constructs were used to assess effects of E1A proteins on AR-mediated transcription. Read More

View Article and Full-Text PDF
November 2018

Effect of melatonin on neuronal differentiation requires CBP/p300-mediated acetylation of histone H3 lysine 14.

Neuroscience 2017 Nov 4;364:45-59. Epub 2017 Aug 4.

Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. Electronic address:

The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties. Read More

View Article and Full-Text PDF
November 2017

The interaction of adenovirus E1A with the mammalian protein Ku70/XRCC6.

Virology 2017 01 19;500:11-21. Epub 2016 Oct 19.

Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2. Electronic address:

Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. Read More

View Article and Full-Text PDF
January 2017

The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Enhances E1A Functional Activity.

mSphere 2016 Jan-Feb;1(1). Epub 2015 Nov 11.

Department of Biochemistry, McGill University, Montreal, Québec, Canada.

Human adenovirus (Ad) E1A proteins have long been known as the central regulators of virus infection as well as the major source of adenovirus oncogenic potential. Not only do they activate expression of other early viral genes, they make viral replication possible in terminally differentiated cells, at least in part, by binding to the retinoblastoma (Rb) tumor suppressor family of proteins to activate E2F transcription factors and thus viral and cellular DNA synthesis. We demonstrate in an accompanying article (F. Read More

View Article and Full-Text PDF

Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma.

Leuk Lymphoma 2016 11 22;57(11):2661-71. Epub 2016 Mar 22.

a Department of Biology , Boston University , Boston , MA , USA.

Mutations in histone acetyltransferases (HATs) are among the most common mutations in diffuse large B-cell lymphoma (DLBCL). We previously showed that two human DLBCL cell lines, RC-K8 and SUDHL2, express C-terminally truncated, HAT domain-deficient p300 proteins (p300ΔC) that are required for optimal cell proliferation. Microarray analysis of mRNA expression in RC-K8 cells following p300ΔC knockdown shows upregulation of NF-κB and p53 gene expression programs and downregulation of a MYC gene expression program. Read More

View Article and Full-Text PDF
November 2016

Effects of Adenovirus Type 5 E1A Isoforms on Viral Replication in Arrested Human Cells.

PLoS One 2015 8;10(10):e0140124. Epub 2015 Oct 8.

Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, Manitoba, R3T 2N2, Canada.

Human adenovirus has evolved to infect and replicate in terminally differentiated human epithelial cells, predominantly those within the airway, the gut, or the eye. To overcome the block to viral DNA replication present in these cells, the virus expresses the Early 1A proteins (E1A). These immediate early proteins drive cells into S-phase and induce expression of all other viral early genes. Read More

View Article and Full-Text PDF

Hypoxia-induced DNp73 stabilization regulates Vegf-A expression and tumor angiogenesis similar to TAp73.

Cell Cycle 2015 ;14(22):3533-9

a Division of Cellular & Molecular Research; Humphrey Oei Institute of Cancer Research; National Cancer Centre ; Singapore.

P73, the homolog of p53, exists in 2 major forms: either as a pro-apoptotic TAp73 or an amino-terminally truncated DNp73, the latter lacking the first transactivation domain. While TAp73s tumor suppressive functions have been established, DNp73 is an anti-apoptotic protein conferring chemoresistance and is associated with poor survival. However, both forms are variably overexpressed in many human cancers. Read More

View Article and Full-Text PDF
September 2016

A rearranged EP300 gene in the human B-cell lymphoma cell line RC-K8 encodes a disabled transcriptional co-activator that contributes to cell growth and oncogenicity.

Cancer Lett 2011 Mar 12;302(1):76-83. Epub 2011 Jan 12.

Department of Biology, Boston University, Boston, MA 02215, USA.

Human diffuse large B-cell lymphoma cell line RC-K8 has an altered EP300 locus that encodes a C-terminally truncated histone acetyltransferase (HAT) protein (p300ΔC). We now show that p300ΔC contains 1047N-terminal amino acids of p300 fused to 25 amino acids encoded by sequences from chromosome 6. Over-expressed p300ΔC localized to nuclear subdomains and interacted with transcription factor REL. Read More

View Article and Full-Text PDF

The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency.

Biochim Biophys Acta 2010 Sep 4;1802(9):754-64. Epub 2010 Jun 4.

Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, Murcia, Spain.

Wild type and dystrophic (merosin-deficient) Lama2dy mice muscles were compared for their density of lipid rafts. The 5-fold higher level of caveolin-3 and the 2-3 times higher level of ecto-5'-nucleotidase activity in raft preparations (Triton X-100-resistant membranes) of dystrophic muscle supported expansion of caveolar and non-caveolar lipid rafts. The presence in rafts of glycosylphosphatidylinositol (GPI)-linked acetylcholinesterase (AChE) dimers, which did not arise from erythrocyte or nerve, not only revealed for the first time the capacity of the myofibre for translating the AChE-H mRNA but also an unrecognized pathway for targeting AChE-H to specialized membrane domains of the sarcolemma. Read More

View Article and Full-Text PDF
September 2010

DNA replication is intrinsically hindered in terminally differentiated myotubes.

PLoS One 2010 Jul 13;5(7):e11559. Epub 2010 Jul 13.

Department of Cell Biology and Neurosciences, National Institute of Health, Rome, Italy.

Background: Terminally differentiated (TD) cells permanently exit the mitotic cycle while acquiring specialized characteristics. Although TD cells can be forced to reenter the cell cycle by different means, they cannot be made to stably proliferate, as attempts to induce their replication constantly result in cell death or indefinite growth arrest. There is currently no biological explanation for this failure. Read More

View Article and Full-Text PDF

Human papillomavirus type 16 E7 oncoprotein associates with E2F6.

J Virol 2008 Sep 25;82(17):8695-705. Epub 2008 Jun 25.

Department of Medicine, Infectious Diseases Division, The Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

The papillomavirus life cycle is intimately coupled to the differentiation state of the infected epithelium. Since papillomaviruses lack most of the rate-limiting enzymes required for genome synthesis, they need to uncouple keratinocyte differentiation from cell cycle arrest and maintain or reestablish a replication-competent state within terminally differentiated keratinocytes. The human papillomavirus (HPV) E7 protein appears to be a major determinant for this activity and induces aberrant S-phase entry through the inactivation of the retinoblastoma tumor suppressor and related pocket proteins. Read More

View Article and Full-Text PDF
September 2008

A cancer-specific transcriptional signature in human neoplasia.

J Clin Invest 2005 Nov 13;115(11):3015-25. Epub 2005 Oct 13.

IFOM, Istituto Fondazione Italiana per la Ricerca sul Cancro di Oncologia Molecolare, Milan, Italy.

The molecular anatomy of cancer cells is being explored through unbiased approaches aimed at the identification of cancer-specific transcriptional signatures. An alternative biased approach is exploitation of molecular tools capable of inducing cellular transformation. Transcriptional signatures thus identified can be readily validated in real cancers and more easily reverse-engineered into signaling pathways, given preexisting molecular knowledge. Read More

View Article and Full-Text PDF
November 2005

Transcriptional regulation of dentin matrix protein 1 by JunB and p300 during osteoblast differentiation.

J Biol Chem 2004 Oct 11;279(43):44294-302. Epub 2004 Aug 11.

Department of Oral Biology, College of Dentistry, University of Illinois, Chicago, Illinois 60612, USA.

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein localized specifically in the mineralized matrix of bone and dentin. Expression analyses demonstrate that DMP1 is differentially regulated in osteoblasts and odontoblasts. Earlier we have reported on the transcriptional regulation of DMP1 by c-Fos and c-Jun (AP-1) transcription factors. Read More

View Article and Full-Text PDF
October 2004

deltaNp73 facilitates cell immortalization and cooperates with oncogenic Ras in cellular transformation in vivo.

Mol Cell Biol 2003 Aug;23(16):5540-55

Department of Pathology, Stony Brook University, Stony Brook, New York 11794, USA.

TP73, despite significant homology to TP53, is not a classic tumor suppressor gene, since it exhibits upregulation of nonmutated products in human tumors and lacks a tumor phenotype in p73-deficient mice. We recently reported that an N-terminally truncated isoform, DeltaNp73, is upregulated in breast and gynecological cancers. We further showed that DeltaNp73 is a potent transdominant inhibitor of wild-type p53 and TAp73 in cultured human tumor cells by efficiently counteracting their target gene transactivations, apoptosis, and growth suppression functions (A. Read More

View Article and Full-Text PDF

Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry.

J Cell Biol 2002 Jun 10;157(6):909-14. Epub 2002 Jun 10.

The FIRC Institute for Molecular Oncology, 20134 Milan, Italy.

Terminal differentiation exerts a remarkably tight control on cell proliferation. However, the oncogenic products of DNA tumor viruses, such as adenovirus E1A, can force postmitotic cells to proliferate, thus representing a powerful tool to study progression into S phase. In this study, we identified the gene encoding Np95, a murine nuclear phosphoprotein, as an early target of E1A-induced transcriptional events. Read More

View Article and Full-Text PDF

Characterization of promoter function and cell-type-specific expression from viral vectors in the nervous system.

J Virol 2000 Dec;74(23):11254-61

Department of Neurology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Viral vectors have become important tools to effectively transfer genes into terminally differentiated cells, including neurons. However, the rational for selection of the promoter for use in viral vectors remains poorly understood. Comparison of promoters has been complicated by the use of different viral backgrounds, transgenes, and target tissues. Read More

View Article and Full-Text PDF
December 2000

p21 and retinoblastoma protein control the absence of DNA replication in terminally differentiated muscle cells.

J Cell Biol 2000 Apr;149(2):281-92

Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

During differentiation, skeletal muscle cells withdraw from the cell cycle and fuse into multinucleated myotubes. Unlike quiescent cells, however, these cells cannot be induced to reenter S phase by means of growth factor stimulation. The studies reported here document that both the retinoblastoma protein (Rb) and the cyclin-dependent kinase (cdk) inhibitor p21 contribute to this unresponsiveness. Read More

View Article and Full-Text PDF

Long-term fate of terminally differentiated skeletal muscle cells following E1A-initiated cell cycle reactivation.

Cell Death Differ 2000 Feb;7(2):145-54

Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome, Italy.

We have previously shown that E1A reactivates the cell cycle in 'irreversibly' growth arrested, terminally differentiated (TD) cells. The molecular events following E1A-mediated reactivation of TD skeletal muscle cells have been extensively investigated. However, the long-term fate of the reactivated cells has not been directly determined. Read More

View Article and Full-Text PDF
February 2000

E2F activates late-G1 events but cannot replace E1A in inducing S phase in terminally differentiated skeletal muscle cells.

Oncogene 1999 Sep;18(36):5054-62

Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome, Italy.

We have previously shown that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. Current models imply that much or all of this E1A activity is mediated by the release of the E2F transcription factors from pocket-protein control. In contrast, we show here that overexpression of E2F-1, E2F-2 and E2F-4, or a chimeric E2F-4 tethered to a nuclear localization signal cannot reactivate postmitotic skeletal muscle cells (myotubes). Read More

View Article and Full-Text PDF
September 1999

Involvement of CREB binding protein in expression of major histocompatibility complex class II genes via interaction with the class II transactivator.

Mol Cell Biol 1998 Nov;18(11):6777-83

Department of Biology, University of Crete, Heraklion, Crete, Greece.

The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) class II genes that are essential components for antigen presentation and thus regulation of the immune response. We show here that the adenovirus E1A protein interferes with the action of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-gamma)-induced expression of MHC class II promoters. Transfection studies provide evidence for the functional role of the CREB-binding protein (CBP) in IFN-gamma and CIITA-mediated MHC class II promoter activation. Read More

View Article and Full-Text PDF
November 1998

Regulation of E2F4 mitogenic activity during terminal differentiation by its heterodimerization partners for nuclear translocation.

Cancer Res 1998 Apr;58(7):1325-31

Laboratory of Gene Expression, Fondazione Andrea Cesalpino, Policlinico Umberto I, University of Rome La Sapienza, Italy.

E2F/DP heterodimers play a pivotal role in the regulation of cell growth and differentiation. A decrease in E2F/DP activity occurs during cell cycle arrest and differentiation. However, very little is known about the specific role of the various E2F/DP members along the transition from proliferation to terminal differentiation. Read More

View Article and Full-Text PDF

Synergistic role of E1A-binding proteins and tissue-specific transcription factors in differentiation.

J Cell Biochem 1997 Dec;67(4):423-31

Kimmel Cancer Center, Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

In this review, the complex relationship between tissue-specific transcription factors and genes regulating cell cycle is taken into account. Both E1-A binding proteins belonging to the family of the retinoblastoma gene product and the CBP/p300 coactivator of transcription interact physically and functionally with tissue-specific transcription factor. The relationship between these two classes of molecules regulates cell fate in differentiating cells, deciding whether cells continue to replicate, undergo apoptosis or terminally differentiate. Read More

View Article and Full-Text PDF
December 1997

Transcriptional coactivator p300 stimulates cell type-specific gene expression in cardiac myocytes.

J Biol Chem 1997 Aug;272(32):20049-54

Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Terminal differentiation is characterized by cell cycle arrest and the expression of cell type-specific genes. Previous work has suggested that the p300 family of transcriptional coactivators plays an important role in preventing the re-initiation of DNA synthesis in terminally differentiated cardiac myocytes. In this study, we investigated whether p300 proteins are also involved in the transcriptional activation of cell type-specific genes in these cells. Read More

View Article and Full-Text PDF

Characterization of an E2F-p130 complex formed during growth arrest.

Oncogene 1997 Aug;15(6):657-68

Department of Biochemistry, McGill University, Montréal, Québec, Canada.

Electrophoretic mobility shift assays were used to analyse the pattern of E2F transcription factor complexes containing pRB and related 'pocket' proteins associated with changes in growth of monkey CV-1 cells. Little change was noted in pRB/E2F complexes following growth arrest or serum stimulation. Serum starvation induced the formation of a novel slowly-migrating p130/E2F complex, termed C7, which was comparable to one reported previously in terminally differentiated C2C12 mouse cells (Corbeil et al. Read More

View Article and Full-Text PDF

The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation.

M M Witte R E Scott

Proc Natl Acad Sci U S A 1997 Feb;94(4):1212-7

Department of Pathology, University of Tennessee Medical Center, Memphis 38163, USA.

Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Read More

View Article and Full-Text PDF
February 1997

Expression of E1A in terminally differentiated muscle cells reactivates the cell cycle and suppresses tissue-specific genes by separable mechanisms.

Mol Cell Biol 1996 Oct;16(10):5302-12

Molecular Oncogenesis Laboratory, Regina Elena Cancer Center, Rome, Italy.

Terminally differentiated cells are characterized by permanent withdrawal from the cell cycle; they do not enter S phase even when stimulated by growth factors or retroviral oncogenes. We have shown, however, that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. In this report, we describe the molecular events triggered by E1A in terminally differentiated skeletal muscle cells. Read More

View Article and Full-Text PDF
October 1996

Terminally differentiated skeletal myotubes are not confined to G0 but can enter G1 upon growth factor stimulation.

Cell Growth Differ 1996 Aug;7(8):1039-50

Molecular Oncogenesis Laboratory Regina Elena Cancer Center, Rome, Italy.

Terminally differentiated cells are specialized cells unable to proliferate that constitute most of the mammalian body. Despite their abundance, little information exists on the characteristics of cell cycle control in these cells and the molecular mechanisms that prevent their proliferation. They are generally believed to be irreversibly restricted to the G0 state. Read More

View Article and Full-Text PDF

Induction of DNA synthesis and apoptosis in cardiac myocytes by E1A oncoprotein.

Y Liu R N Kitsis

J Cell Biol 1996 Apr;133(2):325-34

Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Beginning during the second half of gestation, increasing numbers of cardiac myocytes withdraw from the cell cycle such that DNA synthesis is no longer detectable in these cells by neonatal day 17 in vivo. The mechanisms that exclude these and other terminally differentiated cells from the cell division cycle are poorly understood. To begin to explore the molecular basis of the barrier to G1/S progression in cardiac myocytes, we used adenoviruses to express wild-type and mutant E1A proteins in primary cultures from embryonic day 20 rats. Read More

View Article and Full-Text PDF

The N-terminal region of the adenovirus type 5 E1A proteins can repress expression of cellular genes via two distinct but overlapping domains.

J Virol 1995 May;69(5):2962-7

Department of Medical Biochemistry, Sylvius Laboratory, Leiden, The Netherlands.

The transforming E1A 12S and E1A 13S proteins of human adenovirus type 5 (Ad5) contain two and three conserved regions, respectively. In the present study, the contribution of sequences in the nonconserved N-terminal region of the E1A proteins to morphological transformation and to down-regulation of a number of mitogen-inducible genes was investigated. As described previously, transformation of NRK cells (an established normal rat kidney cell line) results in denser cell growth and a cuboidal cellular morphology. Read More

View Article and Full-Text PDF

Mitotic cycle reactivation in terminally differentiated cells by adenovirus infection.

J Cell Physiol 1995 Jan;162(1):26-35

Department of Cellular and Developmental Biology, University of Rome La Sapieza, Italy.

Different cell types (e.g., neurons, skeletal and heart myocytes, adipocytes, keratinocytes) undergo terminal differentiation, in which acquisition of specialized functions entails definitive withdrawal from the cell cycle. Read More

View Article and Full-Text PDF
January 1995