Abstract:
:An insulin receptor-like signaling pathway regulates Caenorhabditis elegans metabolism, development, and longevity. Inactivation of the insulin receptor homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head transcription factor alleviates the requirement for signaling through this pathway. We show here that a loss-of-function mutation in pdk-1, the C. elegans homolog of the mammalian Akt/PKB kinase PDK1, results in constitutive arrest at the dauer stage and increased life span; these phenotypes are suppressed by a loss of function mutation in daf-16. An activating mutation in pdk-1 or overexpression of wild-type pdk-1 relieves the requirement for AGE-1 PI3K signaling. Therefore, pdk-1 activity is both necessary and sufficient to propagate AGE-1 PI3K signals in the DAF-2 insulin receptor-like signaling pathway. The activating mutation in pdk-1 requires akt-1 and akt-2 gene activity in order to suppress the dauer arrest phenotype of age-1. This indicates that the major function of C. elegans PDK1 is to transduce signals from AGE-1 to AKT-1 and AKT-2. The activating pdk-1 mutation is located in a conserved region of the kinase domain; the equivalent amino acid substitution in human PDK1 activates its kinase activity toward mammalian Akt/PKB.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Paradis S,Ailion M,Toker A,Thomas JH,Ruvkun Gdoi
10.1101/gad.13.11.1438subject
Has Abstractpub_date
1999-06-01 00:00:00pages
1438-52issue
11eissn
0890-9369issn
1549-5477journal_volume
13pub_type
杂志文章abstract::In Xenopus embryos, a dorsal-ventral patterning gradient is generated by diffusing Chordin/bone morphogenetic protein (BMP) complexes cleaved by BMP1/Tolloid metalloproteinases in the ventral side. We developed a new BMP1/Tolloid assay using a fluorogenic Chordin peptide substrate and identified an unexpected negative...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1839309
更新日期:2009-11-01 00:00:00
abstract::Macrophages play critical roles in events ranging from host defense to obesity and cancer, where they infiltrate affected tissues and orchestrate immune responses in tandem with the remodeling of the extracellular matrix (ECM). Despite the dual roles played by macrophages in inflammation, the functions of macrophage-d...
journal_title:Genes & development
pub_type: 杂志文章
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abstract::Transvection can cause the expression of a gene to be sensitive to the proximity of a homolog. It can account for many cases of intragenic complementation at the Drosophila yellow gene, where one mode of transvection involves the action of enhancers in trans on a promoter present on a separate chromosome. Our goal was...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.3.253
更新日期:1999-02-01 00:00:00
abstract::Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.862101
更新日期:2001-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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abstract::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1149604
更新日期:2004-01-15 00:00:00
abstract::A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deac...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2002-02-15 00:00:00
abstract::By studying neuroectoderm formation in the absence of mesoderm and mesectoderm in mutants of the zygotic genes snail and twist, we have found that the number of neuroblasts is not reduced in these mutants, suggesting that mesoderm and mesectoderm are not essential for the initiation of neural development. The position...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.9.1577
更新日期:1991-09-01 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
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journal_title:Genes & development
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更新日期:2010-11-01 00:00:00
abstract::NF-E1, a DNA-binding protein that recognizes the general consensus motif WGATAR, is the first tissue-specific factor to be identified in erythroid cells. Using a probe from the murine GF-1 (NF-E1) cDNA clone, we isolated three homologous chicken cDNAs: One of these corresponds to an mRNA (NF-E1a) that is abundantly an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.10.1650
更新日期:1990-10-01 00:00:00
abstract::The efficiency of RNA 3'-end formation of spleen necrosis virus (SNV) is determined by the distance between the cap site and the poly(A) site. When the distance between the cap site and the poly(A) site was shorter than 500 bases, only 3-9% of the RNA was polyadenylated at the SNV poly(A) site. However, when the dista...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.12b.2299
更新日期:1990-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1832209
更新日期:2009-12-01 00:00:00
abstract::In somatic cells of Xenopus, transcription of the TFIIIA gene initiates greater than 200 bp upstream from the start site used in oocytes. The resultant mRNA encodes a protein, S-TFIIIA, that is 22 amino acids longer at its amino terminus than the abundant form of TFIIIA in oocytes (O-TFIIIA). S-TFIIIA binds the 5S RNA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.9.1602
更新日期:1990-09-01 00:00:00
abstract::How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these seq...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.177428.111
更新日期:2012-01-01 00:00:00
abstract::The yeast SAS (Something About Silencing) complex and the histone variant H2A.Z have both previously been linked to an antisilencing function at the subtelomeric regions. SAS is an H4 Lys 16-specific histone acetyltransferase complex. Here we demonstrate that the H4 Lys 16 acetylation by SAS is required for efficient ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1439206
更新日期:2006-09-15 00:00:00
abstract::The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping fact...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.227843.113
更新日期:2013-12-15 00:00:00
abstract::Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produc...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.1854909
更新日期:2009-09-15 00:00:00
abstract::Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.11.2085
更新日期:1993-11-01 00:00:00
abstract::Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous temp...
journal_title:Genes & development
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更新日期:2004-06-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.398207
更新日期:2007-02-01 00:00:00
abstract::We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knocko...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.22.2894
更新日期:1996-11-15 00:00:00
abstract::Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arres...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.9.1203
更新日期:1999-05-01 00:00:00
abstract::Lineage commitment studies in mammary glands have focused on identifying cell populations that display stem or progenitor properties. However, the mechanisms that control cell fate have been incompletely explored. Herein we show that zinc finger protein 157 (Zfp157) is required to establish the balance between luminal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.184051.111
更新日期:2012-05-15 00:00:00
abstract::In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subuni...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256958.114
更新日期:2015-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2011-03-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2011-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1588207
更新日期:2007-10-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.233395.113
更新日期:2014-01-15 00:00:00