Abstract:
:Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in stringent selection of AUG as the start codon. The eIF3 binds to the 40S ribosome and promotes recruitment of the ternary complex; however, physical contact between eIF3 and eIF2 has not been observed. We show that yeast eIF5 can bridge interaction in vitro between eIF3 and eIF2 by binding simultaneously to the amino terminus of eIF3 subunit NIP1 and the amino-terminal half of eIF2beta, dependent on a conserved bipartite motif in the carboxyl terminus of eIF5. Additionally, the amino terminus of NIP1 can bind concurrently to eIF5 and eIF1. These findings suggest the occurrence of an eIF3/eIF1/eIF5/eIF2 multifactor complex, which was observed in cell extracts free of 40S ribosomes and found to contain stoichiometric amounts of tRNA(i)(Met). The multifactor complex was disrupted by the tif5-7A mutation in the bipartite motif of eIF5. Importantly, the tif5-7A mutant is temperature sensitive and displayed a substantial reduction in translation initiation at the restrictive temperature. We propose that the multifactor complex is an important intermediate in translation initiation in vivo.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Asano K,Clayton J,Shalev A,Hinnebusch AGdoi
10.1101/gad.831800subject
Has Abstractpub_date
2000-10-01 00:00:00pages
2534-46issue
19eissn
0890-9369issn
1549-5477journal_volume
14pub_type
杂志文章abstract::Transcription factors represent one of the largest groups of proteins regulated by SUMO (small ubiquitin-like modifier) modification, and their sumoylation is usually associated with transcriptional repression. To investigate whether sumoylation plays a general role in regulating transcription in yeast, we determined ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1917910
更新日期:2010-06-15 00:00:00
abstract::The widespread class of RNA viruses that utilize internal ribosome entry sites (IRESs) for translation include poliovirus and Hepatitis C virus. To identify host factors required for IRES-dependent translation and viral replication, we performed a genome-wide RNAi screen in Drosophila cells infected with Drosophila C ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267905
更新日期:2005-02-15 00:00:00
abstract::Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::The ATR (ATM and Rad3-related) kinase and its regulatory partner ATRIP (ATR-interacting protein) coordinate checkpoint responses to DNA damage and replication stress. TopBP1 functions as a general activator of ATR. However, the mechanism by which TopBP1 activates ATR is unknown. Here, we show that ATRIP contains a Top...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1666208
更新日期:2008-06-01 00:00:00
abstract::To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.180968.111
更新日期:2012-02-01 00:00:00
abstract::Accurate and regulated transcription by RNA polymerase II requires the assembly of an initiation complex involving multiple protein-DNA and protein-protein interactions. A key event is binding of TFIID, a complex consisting of TBP and associated factors (TAFs) to the template DNA. The TAF subunits of TFIID carry out d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.22.2747
更新日期:1995-11-15 00:00:00
abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.18.2439
更新日期:1999-09-15 00:00:00
abstract::Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mous...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.187807.112
更新日期:2012-09-15 00:00:00
abstract::The labial (lab) gene of Drosophila melanogaster is necessary for the proper development of the embryonic (larval) and adult head. We have identified the lab transcription unit within the proximal portion of the Antennapedia Complex (ANT-C) by mapping the molecular lesions associated with chromosomally rearranged lab ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.3.399
更新日期:1989-03-01 00:00:00
abstract::Bloom's syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom's syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1609007
更新日期:2007-12-01 00:00:00
abstract::Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.8.1217
更新日期:1998-04-15 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.210427.112
更新日期:2013-03-15 00:00:00
abstract::Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-04-15 00:00:00
abstract::Lethal yellow (Ay) is a mutation at the mouse agouti (a) locus that is associated with an all-yellow coat color, obesity, diabetes, tumors in heterozygotes, and preimplantation embryonic lethality in homozygotes. Previously, we cloned and characterized the wild-type agouti gene and demonstrated that it expresses a 0.8...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7a.1203
更新日期:1993-07-01 00:00:00
abstract::In eubacteria, the ClpS adaptor has been proposed to be essential for degradation of N-end rule substrates by the AAA(+) protease ClpAP. To test this model, we assayed degradation of substrates bearing N-end rule sequences isolated in a genetic screen for efficient degradation tags. ClpS was not vital for degradation ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1511907
更新日期:2007-02-15 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00
abstract::The RAG-1 protein plays an essential role in V(D)j recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of codi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.17.2193
更新日期:1995-09-01 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Serotonin is a bioamine regulating bone mass accrual differently depending on its site of synthesis. It decreases accrual when synthesized in the gut, and increases it when synthesized in the brain. The signal transduction events elicited by gut-derived serotonin once it binds to the Htr1b receptor present on osteobla...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1977210
更新日期:2010-10-15 00:00:00
abstract::Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF) family is composed of complexes that contain either Brg1 or hBrm as the central ATPase; however, these separate complexes have not been compared functionally. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.872801
更新日期:2001-03-01 00:00:00
abstract::Constitutive activation of the Wnt/APC/beta-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control. Here we show ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1260605
更新日期:2005-02-01 00:00:00
abstract::Caenorhabditis elegans GLD-1, a KH motif containing RNA-binding protein of the GSG/STAR subfamily, controls diverse aspects of germ line development, suggesting that it may have multiple mRNA targets. We used an immunoprecipitation/subtractive hybridization/cloning strategy to identify 15 mRNAs that are putative targe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.915901
更新日期:2001-09-15 00:00:00
abstract::Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated by siRNA or chicken DT40 cells with a homozygous deletion of the RNF4 gene displa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.189274.112
更新日期:2012-06-01 00:00:00
abstract::Transcriptional activation of the human U1 snRNA genes is dependent on a noncanonical octamer element contained within an upstream enhancer. The U1 octamer only weakly recruits the Oct-1 POU domain, although recruitment is stimulated by a peptide containing the Oct-1-binding domain of SNAP190. Structural analysis of t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1021002
更新日期:2002-11-01 00:00:00
abstract::Protection of the stalled replication fork is crucial for responding to replication stress and minimizing its impact on chromosome instability, thus preventing diseases, including cancer. We found a new component, Abro1, in the protection of stalled replication fork integrity. Abro1 deficiency results in increased chr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299172.117
更新日期:2017-07-15 00:00:00
abstract::Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.23.2817
更新日期:1994-12-01 00:00:00
abstract::The structurally related POU homeo domain proteins Pit-1 and Oct-2 activate pituitary- and lymphoid-specific transcription, respectively, by binding to similar AT-rich motifs in their target genes. In this study we identify bases critical for recognition and activation by Pit-1 and examine how small differences in Pit...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.43
更新日期:1990-01-01 00:00:00
abstract::The Rho family of small GTPases are critical elements involved in the regulation of signal transduction cascades from extracellular stimuli to the cell nucleus, including the JNK/SAPK signaling pathway, the c-fos serum response factor, and the p70 S6 kinase. Here we report a novel signaling pathway activated by the Rh...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.4.463
更新日期:1997-02-15 00:00:00
abstract::Joints form within the developing skeleton through the segmentation and cavitation of initially continuous cartilage condensations. However, the molecular pathways controlling joint formation largely remain to be clarified. In particular, while several critical secreted signals have been identified, no transcription f...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.209239.112
更新日期:2013-03-01 00:00:00