Abstract:
:Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3' untranslated mRNA stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Vumbaca F,Phoenix KN,Rodriguez-Pinto D,Han DK,Claffey KPdoi
10.1128/MCB.02078-06subject
Has Abstractpub_date
2008-01-01 00:00:00pages
772-83issue
2eissn
0270-7306issn
1098-5549pii
MCB.02078-06journal_volume
28pub_type
杂志文章abstract::We have examined the possible role of adenosine 3',5'-phosphate (cAMP) in functions associated with the plasma membranes of Saccharomyces cerevisiae. Purified membranes from this source contained an adenylate cyclase which was insensitive to activation by fluoride or guanine nucleotides, only weakly responsive to chan...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.12.1481
更新日期:1982-12-01 00:00:00
abstract::Determining the roles of Rel/NF-kappaB transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor n...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.13.5733-5745.2004
更新日期:2004-07-01 00:00:00
abstract::Ribosome biogenesis in eukaryotes is a major cellular activity mobilizing the products of over 200 transcriptionally coregulated genes referred to as the rRNA and ribosome biosynthesis regulon. We investigated the function of an essential, uncharacterized gene of this regulon, renamed RRP36. We show that the Rrp36p pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00999-09
更新日期:2010-03-01 00:00:00
abstract::The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicke...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.5756
更新日期:1994-09-01 00:00:00
abstract::Angiotensin II (AII), a potent vasoactive hormone, acts on numerous organs via G-protein-coupled receptors and elicits cell-specific responses. At the level of the heart, AII stimulation alters gene transcription and leads to cardiomyocyte hypertrophy. Numerous intracellular signaling pathways are activated in this pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.22.9829-9844.2005
更新日期:2005-11-01 00:00:00
abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00552-06
更新日期:2006-08-01 00:00:00
abstract::Viruses have developed numerous strategies to counteract the host cell defense. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA tumor virus linked to the development of Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma (PEL). The virus-encoded viral interferon regulatory factor 3 (vIRF-3) ge...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01011-13
更新日期:2014-02-01 00:00:00
abstract::Only a fraction of retroviral primary transcripts are spliced to subgenomic mRNAs; the unspliced transcripts are transported to the cytoplasm for packaging into virions and for translation of the gag and pol genes. We identified cis-acting sequences within the gag gene of Rous sarcoma virus (RSV) which negatively regu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.11.4858
更新日期:1988-11-01 00:00:00
abstract::Xenopus laevis oogenesis is characterized by an active transcription which ceases abruptly upon maturation. To survey changes in the characteristics of the transcriptional machinery which might contribute to this transcriptional arrest, the phosphorylation status of the RNA polymerase II largest subunit (RPB1 subunit)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.3.1434
更新日期:1997-03-01 00:00:00
abstract::ZO-1, ZO-2, and ZO-3 are closely related MAGUK family proteins that localize at the cytoplasmic surface of tight junctions (TJs). ZO-1 and ZO-2 are expressed in both epithelia and endothelia, whereas ZO-3 is exclusively expressed in epithelia. In spite of intensive studies of these TJ MAGUKs, our knowledge of their fu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01811-05
更新日期:2006-12-01 00:00:00
abstract::Two cis-regulatory regions are required for efficient mRNA 3'-end processing of the maize 27-kDa zein mRNA: a region containing a duplicated AAUGAA poly(A) signal and a region that is present upstream from it. Strict spatial positioning of these two regions is required for efficient mRNA 3'-end processing. Insertion o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6829
更新日期:1994-10-01 00:00:00
abstract::Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), and Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. To investigate the potential role of specific interactions between these enzymes during signaling, their ability to associate with each...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.7.3637
更新日期:1996-07-01 00:00:00
abstract::We previously identified a sequence-specific erythroid cell-enriched endoribonuclease (ErEN) activity involved in the turnover of the stable alpha-globin mRNA. We now demonstrate that ErEN activity is regulated by the poly(A) tail. The unadenylated alpha-globin 3' untranslated region (3'UTR) was an efficient substrate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.17.6334-6341.2000
更新日期:2000-09-01 00:00:00
abstract::Loss of heterozygosity (LOH) is a common genetic alteration in tumors and often extends several megabases to encompass multiple genetic loci or even whole chromosome arms. Based on marker and karyotype analysis of tumor samples, a significant fraction of LOH events appears to arise from mitotic recombination between h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.2.733-743.2003
更新日期:2003-01-01 00:00:00
abstract::The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosop...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.8.4295
更新日期:1996-08-01 00:00:00
abstract::Precursor RNA containing the adenovirus L3 polyadenylation site is assembled into a 50S complex upon incubation with HeLa nuclear extract at 30 degrees C. The cofactor and sequence requirements for 50S complex formation are similar to those of the in vitro polyadenylation reaction. Assembly of this complex requires AT...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.226
更新日期:1988-01-01 00:00:00
abstract::Lipophilic compounds such as retinoic acid and long-chain fatty acids regulate gene transcription by activating nuclear receptors such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). These compounds also bind in cells to members of the family of intracellular lipid binding pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.14.5114-5127.2002
更新日期:2002-07-01 00:00:00
abstract::Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.4.2352
更新日期:1994-04-01 00:00:00
abstract::We have studied the patterns of expression of four B-type cyclins (Clbs), Clb1, Clb2, Clb3, and Clb4, and their ability to activate p34cdc28 during the mitotic and meiotic cell cycles of Saccharomyces cerevisiae. During the mitotic cell cycle, Clb3 and Clb4 were expressed and induced a kinase activity in association w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.4.2113
更新日期:1993-04-01 00:00:00
abstract::Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00983-10
更新日期:2011-02-01 00:00:00
abstract::GCN4 encodes a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. The GCN3 product is a positive regulator required for increased synthesis of GCN4 protein in amino acid-starved cells. GCN3 appears to act indirectly by antagonizing GCD-encoded negative regulators of GCN4 expression...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.11.4808
更新日期:1988-11-01 00:00:00
abstract::The accumulation of assembled holoenzymes composed of regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase of the cell cycle in mammalian fibroblasts. Both the synthesis and assembly of D-type cyclins and cdk4 depend upon serum s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.4.2713
更新日期:1994-04-01 00:00:00
abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.169
更新日期:1989-01-01 00:00:00
abstract::Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. To gain a comprehensive understanding of the roles of Spt6, we performed genome-wide analyses of transcription, chromatin structure, and histone modifications in a Schizosaccharomy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01068-13
更新日期:2013-12-01 00:00:00
abstract::Transcription by RNA polymerase I (pol I), pol II, and pol III requires the TATA-binding protein (TBP). This protein functions in association with distinct TBP-associated factors (TAFs) which may specify the nature of the polymerase selected for initiation at a promoter site. In the pol III transcription system, the T...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.12.7953
更新日期:1993-12-01 00:00:00
abstract::The FLP protein of the Saccharomyces cerevisiae plasmid 2 microns circle catalyzes site-specific recombination between two repeated segments present on the plasmid. In this paper we present results of experiments we performed to define more precisely the features of the FLP recognition target site, which we propose to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3357
更新日期:1986-10-01 00:00:00
abstract::The human Ki-ras gene was previously reported to contain two alternative fourth exons which encode two distinct p21 proteins differing only at their carboxy termini. The present study shows that either p21 protein is able on its own to transform NIH 3T3 cells to a tumorigenic state. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.4.1326
更新日期:1986-04-01 00:00:00
abstract::Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein Gα(i) subunits to exchange GDP for GTP. By limiting the duration that Gα(i) su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00651-12
更新日期:2012-11-01 00:00:00
abstract::Substitution of phenylalanine for tyrosine at codon 809 (Y809F) of the human colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) impairs ligand-stimulated tyrosine kinase activity, prevents induction of c-MYC and cyclin D1 genes, and blocks CSF-1-dependent progression through the G1 phase of the cell cycle. We devis...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.12.7398
更新日期:1997-12-01 00:00:00
abstract::Studies were undertaken to determine the effect of the Ras suppressor Rsu-1 on Ras signal transduction pathways in two different cell backgrounds. An expression vector containing the mouse rsu-1 cDNA under the control of a mouse mammary tumor virus promoter was introduced into NIH 3T3 cells and the pheochromocytoma ce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.10.5466
更新日期:1996-10-01 00:00:00