Abstract:
:The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G(1) phase to S phase. Although the signaling events after growth factor stimulation have been well characterized, it is not yet clear how these signals contact the cell cycle machinery. We had found previously that growth factor stimulation of quiescent cells lead to the direct binding of Raf-1 kinase to Rb, leading to its inactivation. Here we show that the Rb-Raf-1 interaction occurs prior to the activation of cyclin and/or cyclin-dependent kinases and facilitates normal cell cycle progression. Raf-1-mediated inactivation of Rb is independent of the mitogen-activated protein kinase cascade, as well as cyclin-dependent kinases. Binding of Raf-1 seemed to correlate with the dissociation of the chromatin remodeling protein Brg1 from Rb. Disruption of the Rb-Raf-1 interaction by a nine-amino-acid peptide inhibits Rb phosphorylation, cell proliferation, and vascular endothelial growth factor-mediated capillary tubule formation. Delivery of this peptide by a carrier molecule led to a 79% reduction in tumor volume and a 57% reduction in microvessel formation in nude mice. It appears that Raf-1 links mitogenic signaling to Rb and that disruption of this interaction could aid in controlling proliferative disorders.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Dasgupta P,Sun J,Wang S,Fusaro G,Betts V,Padmanabhan J,Sebti SM,Chellappan SPdoi
10.1128/MCB.24.21.9527-9541.2004subject
Has Abstractpub_date
2004-11-01 00:00:00pages
9527-41issue
21eissn
0270-7306issn
1098-5549pii
24/21/9527journal_volume
24pub_type
杂志文章abstract::Ribosomes can be programmed to shift from one reading frame to another during translation. Hepatitis C virus (HCV) uses such a mechanism to produce F protein from the -2/+1 reading frame. We now report that the HCV frameshift signal can mediate the synthesis of the core protein of the zero frame, the F protein of the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.5.1489-1497.2003
更新日期:2003-03-01 00:00:00
abstract::Analysis of a T-cell antigen receptor (TCR) alpha promoter from a variable gene segment (V) revealed a critical GT box element which is also found in upstream regions of several V alpha genes, TCR enhancer, and regulatory elements of other genes. This element is necessary for TCR gene expression and binds several prot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.10.4251
更新日期:1992-10-01 00:00:00
abstract::The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5262-5275.2001
更新日期:2001-08-01 00:00:00
abstract::The minichromosome maintenance protein 10 (Mcm10) is an evolutionarily conserved factor that is essential for replication initiation and elongation. Mcm10 is part of the eukaryotic replication fork and interacts with a variety of proteins, including the Mcm2-7 helicase and DNA polymerase alpha/primase complexes. A mot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02062-05
更新日期:2006-07-01 00:00:00
abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.01454-13
更新日期:2014-04-01 00:00:00
abstract::Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal part...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00358-10
更新日期:2010-09-01 00:00:00
abstract::TRIF is an essential adaptor for Toll-like receptor 3/4 (TLR3/4) signaling to activate transcription factor interferon regulatory factor 3 (IRF-3). We examined the molecular mechanism of TLR3 signaling and found that TLR3 stimulation by double-stranded RNA (dsRNA) induces phosphorylation of TRIF at Ser210 and is requi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00509-19
更新日期:2020-02-12 00:00:00
abstract::A sequence-specific DNA-binding protein from skeletal-muscle extracts that binds to probes of three muscle gene DNA elements is identified. This protein, referred to as muscle factor 3, forms the predominant nucleoprotein complex with the MCAT gene sequence motif in an electrophoretic mobility shift assay. This protei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.1944
更新日期:1991-04-01 00:00:00
abstract::The 2 micron plasmid of Saccharomyces cerevisiae codes for a site-specific recombinase, the FLP protein, that catalyzes efficient recombination across two 599-base-pair (bp) inverted repeats of the plasmid DNA both in vivo and in vitro. We analyzed the interaction of the purified FLP protein with the target sequences ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2482
更新日期:1986-07-01 00:00:00
abstract::We have constructed a size variant of the Drosophila hsp28 gene by deleting 207 base pairs of the protein coding region, beginning 33 base pairs downstream of the ATG protein initiation codon. After transformation of Drosophila melanogaster rosy (ry506) flies with this altered gene, using the P transposable element sy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.12.2883
更新日期:1984-12-01 00:00:00
abstract::Cloned segments of the mouse glycerol-3-phosphate dehydrogenase (GPDH) gene, Gdc-1, were used to screen a human library. Human clones obtained spanned 25 kilobases of genomic DNA containing the human GPDH gene, GPD1. The 4 kb of sequence obtained from the 5'-flanking region and first exon of GPD1 was compared with the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.10.5244
更新日期:1990-10-01 00:00:00
abstract::We have investigated the kinds of mutations induced when a shuttle vector containing covalently bound residues of the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) replicates in the monkey kidney cell line COS7. The target for detecting mutations was the 200-base pair g...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1267
更新日期:1987-03-01 00:00:00
abstract::Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice and cells derived from them showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00945-06
更新日期:2006-12-01 00:00:00
abstract::In an effort to identify aberrantly expressed genes in v-rel-induced tumors, monoclonal antibodies were developed that reacted selectively with avian B-cell tumors. One antibody, HY78, immunoprecipitated a 120-kDa glycoprotein (p120) from cells that express v-rel. N-terminal amino acid sequencing of p120 identified a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1806
更新日期:1995-03-01 00:00:00
abstract::Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place. A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.3136
更新日期:1999-04-01 00:00:00
abstract::The Ace2p and Swi5p zinc finger proteins have nearly identical DNA-binding domains, yet in vivo they activate transcription of different genes, CTS1 and HO. We now demonstrate that Ace2p and Swi5p recognize sites in the CTS1 and HO promoters with the same affinities, raising the question of how promoter specificity is...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.4.1746
更新日期:1996-04-01 00:00:00
abstract::The Ras pathway is critical for the development and function of T lymphocytes. The stimulation of this GTPase in T cells occurs primarily through the Vav1- and phospholipase C-gamma1-dependent activation of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor. Here, we show that a second exchange factor, R...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00912-07
更新日期:2007-12-01 00:00:00
abstract::A gene encoding a novel CACCC box-binding protein that binds to the promoter region of the human T-cell receptor (TCR) V beta 8.1 gene and the mouse TCR alpha gene silencer has been cloned. This gene, termed ht beta, contains four zinc fingers of the class Cys2-X12-His2 that may be responsible for DNA binding and a hi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5691
更新日期:1993-09-01 00:00:00
abstract::The yeast mitochondrial DNA group II introns aI1 and aI2 are retroelements that insert site specifically into intronless alleles by a process called homing. Here, we used patterns of flanking marker coconversion in crosses with wild-type and mutant aI2 introns to distinguish three coexisting homing pathways: two that ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.22.8432-8446.2000
更新日期:2000-11-01 00:00:00
abstract::The human immunodeficiency virus type 1 Rev protein contains a nuclear export signal (NES) that is required for Rev-mediated RNA export in mammals as well as in the yeast Saccharomyces cerevisiae. The Rev NES has been shown to specifically interact with a human (hRIP/RAB1) and a yeast (yRip1p) protein in the two-hybri...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.12.7144
更新日期:1996-12-01 00:00:00
abstract::IkappaB alpha retains the transcription factor NF-kappaB in the cytoplasm, thus inhibiting its function. Various stimuli inactivate IkappaB alpha by triggering phosphorylation of the N-terminal residues Ser32 and Ser36. Phosphorylation of both serines is demonstrated directly by phosphopeptide mapping utilizing calpai...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.6.3021
更新日期:1997-06-01 00:00:00
abstract::Topoisomerase I cleavage complexes can be induced by a variety of DNA damages and by the anticancer drug camptothecin. We have developed a ligation-mediated PCR (LM-PCR) assay to analyze replication-mediated DNA double-strand breaks induced by topoisomerase I cleavage complexes in human colon carcinoma HT29 cells at t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.11.3977-3987.2000
更新日期:2000-06-01 00:00:00
abstract::E2F and RB proteins regulate the expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. Recent studies indicate that they function as part of an evolutionarily conserved multiprotein complex termed dREAM/DREAM/LINC. Here we characterize the role of the Drosophila complex, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06314-11
更新日期:2012-06-01 00:00:00
abstract::Polycomb group proteins mediate heritable transcriptional silencing and function through multiprotein complexes that methylate and ubiquitinate histones. The 600-kDa E(Z)/ESC complex, also known as Polycomb repressive complex 2 (PRC2), specifically methylates histone H3 lysine 27 (H3 K27) through the intrinsic histone...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01822-06
更新日期:2007-03-01 00:00:00
abstract::The uptake of various nucleosides by S49 mouse T-lymphoma cells and that by a single-step nucleoside transport-defective mutant thereof (AE1) were compared. Residual nucleoside entry into AE1 cells occurred via two routes, nonmediated permeation and saturable, non-concentrative transport with broad substrate specifici...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.1.160
更新日期:1987-01-01 00:00:00
abstract::The alpha 2 protein of the yeast Saccharomyces cerevisiae normally represses a set of cell-type-specific genes (the a-specific genes) that are transcribed by RNA polymerase II. In this study, we determined whether alpha 2 can affect transcription by other RNA polymerases. We find that alpha 2 can repress transcription...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.7.4029
更新日期:1993-07-01 00:00:00
abstract::We describe experiments which demonstrated that the simian virus 40 (SV40) enhancer affects certain transcriptional units differently. We also found that a specific enhancer-transcriptional unit interaction can be regulated by trans-acting factors. Using transient assays, we examined the effects of the SV40 enhancer o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.4.1283
更新日期:1986-04-01 00:00:00
abstract::Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00898-15
更新日期:2015-11-02 00:00:00
abstract::Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55alpha and p55gamma) regulatory subun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.5.1717-1725.2003
更新日期:2003-03-01 00:00:00
abstract::The punc gene, encoding a member of the neural cell adhesion molecule family expressed in the developing central nervous system, limbs, and inner ear, was identified. To extend studies of the normal expression pattern of punc and to determine its function, a mouse strain bearing a lacZ/neo insertion in a 5' coding exo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.21.17.6031-6043.2001
更新日期:2001-09-01 00:00:00