Abstract:
:The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism Murr1 Domain 1 (COMMD1) and Cul2. We report here that GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses kappaB-dependent transcription. In this role, the acetyltransferase activity of GCN5 is not required. Interestingly, GCN5 binds more avidly to RelA after phosphorylation on Ser 468, an event that is dependent on IKK activity. Consistent with this, we find that both GCN5 and the IkappaB Kinase (IKK) complex promote RelA degradation. Collectively, the data indicate that GCN5 participates in the ubiquitination process as an accessory factor for a ubiquitin ligase, where it provides a novel link between phosphorylation and ubiquitination.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Mao X,Gluck N,Li D,Maine GN,Li H,Zaidi IW,Repaka A,Mayo MW,Burstein Edoi
10.1101/gad.1748409subject
Has Abstractpub_date
2009-04-01 00:00:00pages
849-61issue
7eissn
0890-9369issn
1549-5477pii
23/7/849journal_volume
23pub_type
杂志文章abstract::Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for api...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.20.3156
更新日期:1998-10-15 00:00:00
abstract::The Drosophila somatic sex-determination regulatory pathway has been well studied, but little is known about the target genes that it ultimately controls. In a differential screen for sex-specific transcripts expressed in fly heads, we identified a highly male-enriched transcript encoding Takeout, a protein related to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1010302
更新日期:2002-11-15 00:00:00
abstract::The Arabidopsis APETALA3 (AP3) and PISTILLATA (PI) proteins are thought to act as transcription factors and are required for specifying floral organ identities. To define the nuclear localization signals within these proteins, we generated translational fusions of the coding regions of AP3 and PI to the bacterial uidA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.14.1812
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abstract::Homeotic genes are expressed in spatially precise patterns during Drosophila development to control segmental differentiation. The Sex combs reduced (Scr) gene of the Antennapedia gene complex is involved in the determination of the labial and prothoracic segments of the embryo. To study both the wild-type pattern of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.716
更新日期:1987-09-01 00:00:00
abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1286005
更新日期:2005-04-01 00:00:00
abstract::Many tumors continuously depend on the initiating oncogenes, but whether this extends to their downstream targets is unclear. In this issue of Genes & Development, Sodir and colleagues (pp. 907-916) demonstrate an essential role for endogenous Myc proteins in maintaining the tumor microenvironment, providing an unexpe...
journal_title:Genes & development
pub_type: 评论,杂志文章
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abstract::In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance...
journal_title:Genes & development
pub_type: 评论,杂志文章
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更新日期:2010-08-01 00:00:00
abstract::The transcription cofactor MAL is regulated by free actin levels and thus by actin dynamics. MAL, together with its DNA-binding partner, SRF, is required for invasive cell migration and in experimental metastasis. Although MAL/SRF has many targets, we provide genetic evidence in both Drosophila and human cellular mode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237743.114
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abstract::Activation of p53-mediated transcription is a critical cellular response to DNA damage. p53 stability and site-specific DNA-binding activity and, therefore, transcriptional activity, are modulated by post-translational modifications including phosphorylation and acetylation. Here we show that p53 is acetylated in vitr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.18.2831
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abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1902110
更新日期:2010-05-01 00:00:00
abstract::Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose depriv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1985910
更新日期:2010-12-15 00:00:00
abstract::Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage. Like its yeast homologs, the Chk2/hCds1 protein phosphorylates Cdc25C in vitro, suggesting that it ar...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on skin keratinocytes, where it is the most potent growth factor identified thus far. To explore KGF's function in vivo, we used embryonic stem cell technology to ge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.2.165
更新日期:1996-01-15 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::An RNA-binding protein gene (rbp1) from Drosophila melanogaster, encoding an RNA recognition motif and an Arg-Ser rich (RS) domain, has been characterized. The predicted amino acid sequence of rbp1 is similar to those of the human splicing factor ASF/SF2, the Drosophila nuclear phosphoprotein SRp55, and the Drosophila...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12b.2569
更新日期:1992-12-01 00:00:00
abstract::Distinctive from that of the animal system, the basic plan of the plant body is the continuous formation of a structural unit, composed of a stem with a meristem at the top and lateral organs continuously forming at the meristem. Therefore, mechanisms controlling the formation, maintenance, and development of a merist...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.9.1079
更新日期:1999-05-01 00:00:00
abstract::Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity acros...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1688508
更新日期:2008-10-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We ha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7b.1364
更新日期:1993-07-01 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::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::The essential splicing factor human UAP56 (hUAP56) is a DExD/H-box protein known to promote prespliceosome assembly. Here, using a series of hUAP56 mutants that are defective for ATP-binding, ATP hydrolysis, or dsRNA unwindase/helicase activity, we assess the relative contributions of these biochemical functions to pr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1657308
更新日期:2008-07-01 00:00:00
abstract::In a four-cell-stage Caenorhabditis elegans embryo, Wnt signaling polarizes an endoderm precursor called EMS. The polarization of this cell orients its mitotic spindle in addition to inducing endodermal fate in one daughter cell. Reducing the function of Wnt pathway genes, including a newly identified GSK-3beta homolo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.15.2028
更新日期:1999-08-01 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::We have analyzed pre-mRNA splicing in yeast extracts immunodepleted of the PRP18 protein. We find that while the first step of splicing (cleavage at the 5' splice site, and generation of the exon 1 and lariat intermediates) is unaffected by the absence of PRP18, the second step of splicing (excision of the lariat intr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.320
更新日期:1993-02-01 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::The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 ar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.305037.117
更新日期:2017-10-15 00:00:00
abstract::A prominent feature of cell differentiation is the initiation and maintenance of an irreversible cell cycle arrest with the complex involvement of the retinoblastoma (RB) family (RB, p130, p107). We have isolated the HBP1 transcriptional repressor as a potential target of the RB family in differentiated cells. By homo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.3.383
更新日期:1997-02-01 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::Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only sequence-specific DNA-binding protein. To gain insight into the function of Pho,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377406
更新日期:2006-05-01 00:00:00
abstract::Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246538.114
更新日期:2014-11-15 00:00:00