Abstract：
:Hypoxia induces rapid and dramatic changes in cellular metabolism, in part through inhibition of target of rapamycin (TOR) kinase complex 1 (TORC1) activity. Genetic studies have shown the tuberous sclerosis tumor suppressors TSC1/2 and the REDD1 protein to be essential for hypoxia regulation of TORC1 activity in Drosophila and in mammalian cells. The molecular mechanism and physiologic significance of this effect of hypoxia remain unknown. Here, we demonstrate that hypoxia and REDD1 suppress mammalian TORC1 (mTORC1) activity by releasing TSC2 from its growth factor-induced association with inhibitory 14-3-3 proteins. Endogenous REDD1 is required for both dissociation of endogenous TSC2/14-3-3 and inhibition of mTORC1 in response to hypoxia. REDD1 mutants that fail to bind 14-3-3 are defective in eliciting TSC2/14-3-3 dissociation and mTORC1 inhibition, while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1. In vitro, loss of REDD1 signaling promotes proliferation and anchorage-independent growth under hypoxia through mTORC1 dysregulation. In vivo, REDD1 loss elicits tumorigenesis in a mouse model, and down-regulation of REDD1 is observed in a subset of human cancers. Together, these findings define a molecular mechanism of signal integration by TSC1/2 that provides insight into the ability of REDD1 to function in a hypoxia-dependent tumor suppressor pathway.
journal_name
Genes Devjournal_title
Genes & developmentauthors
DeYoung MP,Horak P,Sofer A,Sgroi D,Ellisen LWdoi
10.1101/gad.1617608subject
Has Abstractpub_date
2008-01-15 00:00:00pages
239-51issue
2eissn
0890-9369issn
1549-5477pii
22/2/239journal_volume
22pub_type
杂志文章abstract：:The recombination site dif is the target on the Escherichia coli chromosome of the site-specific recombinases XerC and XerD. The dif/XerC-D system plays a role during the cell cycle, probably by favoring sister chromosome monomerization or separation. A phenomenon of regional control over dif activity, also analyzed i...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.10.9.1152
更新日期：1996-05-01 00:00:00
abstract：:Telomere proteins protect the chromosomal terminus from nucleolytic degradation and end-to-end fusion, and they may contribute to telomere length control and the regulation of telomerase. The current studies investigate the effect of Oxytricha single-stranded telomere DNA-binding protein subunits alpha and beta on tel...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.10.1504
更新日期：1998-05-15 00:00:00
abstract：:Overexpression of the type II transmembrane serine protease matriptase is a highly consistent feature of human epithelial tumors. Here we show that matriptase possesses a strong oncogenic potential when unopposed by its endogenous inhibitor, HAI-1. Modest orthotopic overexpression of matriptase in the skin of transgen...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1300705
更新日期：2005-08-15 00:00:00
abstract：:Influenza virus unspliced NS1 mRNA, like retroviral pre-mRNAs, is efficiently exported from the nucleus and translated in the cytoplasm of infected cells. With human immunodeficiency virus (HIV), the transport of viral pre-mRNAs is facilitated by the viral Rev protein. We tested the possibility that the influenza viru...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.2.255
更新日期：1992-02-01 00:00:00
abstract：:A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an en...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.6.993
更新日期：1990-06-01 00:00:00
abstract：:The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1007302
更新日期：2002-09-01 00:00:00
abstract：:The cooperation of oncogenes in the transformation of primary rat Schwann cells is a strikingly synergistic process. We have explored the molecular mechanisms involved. Activation of an inducible Raf kinase results in morphologically transformed cells that are arrested in G1 via the induction of p21(CiP1) and subseque...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.5.663
更新日期：1997-03-01 00:00:00
abstract：:The balance between proliferation and differentiation of muscle stem cells is tightly controlled, ensuring the maintenance of a cellular pool needed for muscle growth and repair. We demonstrate here that the transcriptional regulator Hes1 controls the balance between proliferation and differentiation of activated musc...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.322818.118
更新日期：2019-05-01 00:00:00
abstract：:We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.14.1827
更新日期：1997-07-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.512209
更新日期：2009-03-15 00:00:00
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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：: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：:Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LI...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.181933.111
更新日期：2012-03-01 00:00:00
abstract：:Deletions and other chromosomal rearrangements can be generated by recombination between repeated sequences. It has been shown in a number of systems that the probability of exchange or gene conversion decreases with increasing distance between repeats. This paper examines the question of how repeats find each other, ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.12b.1800
更新日期：1988-12-01 00:00:00
abstract：:Small noncoding RNAs, including small interfering RNAs (siRNAs) and micro RNAs (miRNAs) of approximately 21 nucleotides (nt) in length, have emerged as potent regulators of gene expression at both transcriptional and post-transcriptional levels in diverse organisms. Here we report the identification of a novel class o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1434406
更新日期：2006-07-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.3.356
更新日期：1992-03-01 00:00:00
abstract：:The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with v...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.204776.112
更新日期：2013-01-15 00:00:00
abstract：:Exposure of hematopoietic progenitors to gamma-irradiation (IR) induces p53-dependent apoptosis and a p53-independent G2/M cell cycle arrest. These responses to DNA-damage can be inhibited by treatment with cytokine growth factors. Here we report that gamma-IR-induced apoptosis and cell cycle arrest are suppressed by ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.8.1099
更新日期：1998-04-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1553007
更新日期：2007-08-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.12a.2225
更新日期：1991-12-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.5.626
更新日期：1995-03-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.178962.111
更新日期：2011-12-01 00:00:00
abstract：:Our laboratory has been utilizing the Escherichia coli outer membrane protein LamB to study the mechanism of protein localization. Various lines of evidence suggest that, in addition to a signal sequence, regions within the mature protein are required for efficient localization. In particular, studies using LamB-LacZ ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1.2.185
更新日期：1987-04-01 00:00:00
abstract：:Somatic cell clones often fail at a developmental stage coincident with commencement of differentiation. The transcription factor Oct4 is expressed during cleavage stages and is essential for the differentiation of the blastocyst. Oct4 expression becomes restricted to the inner cell mass and epiblast. After gastrulati...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.966002
更新日期：2002-05-15 00:00:00
abstract：:Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.430107
更新日期：2007-09-01 00:00:00
abstract：:Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice we...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.12.1894
更新日期：1998-06-15 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
pub_type： 杂志文章
doi：10.1101/gad.1204304
更新日期：2004-06-01 00:00:00
abstract：:Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various human cancers, including breast cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.304261.117
更新日期：2017-10-01 00:00:00
abstract：:Ribonucleotide reductase activity is essential for progression through the cell cycle, catalyzing the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis. The enzymatic activity of the enzyme fluctuates in the cell cycle with an activity maximum in S phase. We have identified and cha...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.5.740
更新日期：1990-05-01 00:00:00
abstract：:The activity of the polyoma virus (PyV) origin of DNA replication was used as a sensitive assay for enhancer function in one- and two-cell mouse embryos by injecting embryos with plasmid DNA containing different PyV ori configurations, allowing them to continue development in vitro, and then measuring plasmid DNA repl...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.9.1115
更新日期：1988-09-01 00:00:00
