Abstract:
:Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had a short life span and were prone to spontaneous tumors and liver abnormalities, including steatosis, hepatitis, and hepatocellular carcinoma. We also found that FDXR was necessary for mitochondrial iron homeostasis and proper expression of several master regulators of iron metabolism, including iron regulatory protein 2 (IRP2). Surprisingly, we found that p53 mRNA translation was suppressed by FDXR deficiency via IRP2. Moreover, we found that the signal from FDXR to iron homeostasis and the p53 pathway was transduced by ferredoxin 2, a substrate of FDXR. Finally, we found that p53 played a role in iron homeostasis and was required for FDXR-mediated iron metabolism. Together, we conclude that FDXR and p53 are mutually regulated and that the FDXR-p53 loop is critical for tumor suppression via iron homeostasis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Zhang Y,Qian Y,Zhang J,Yan W,Jung YS,Chen M,Huang E,Lloyd K,Duan Y,Wang J,Liu G,Chen Xdoi
10.1101/gad.299388.117subject
Has Abstractpub_date
2017-06-15 00:00:00pages
1243-1256issue
12eissn
0890-9369issn
1549-5477pii
gad.299388.117journal_volume
31pub_type
杂志文章abstract::Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in S...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.8.959
更新日期:1994-04-15 00:00:00
abstract::The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1399806
更新日期:2006-03-01 00:00:00
abstract::The P family of transposable elements in Drosophila transpose by a cut-and-paste mechanism involving double-strand gap repair. We report here that a Drosophila mutagen-sensitive mutant, mus3O9, contains a mutation in IRBP (inverted repeat binding protein), the Drosophila homolog of the mammalian Ku p70 gene. We show t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.8.921
更新日期:1996-04-15 00:00:00
abstract::The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell sub...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.187328.112
更新日期:2012-04-01 00:00:00
abstract::The crucifer Arabidopsis thaliana has been used widely as a model organism for the study of plant development. We describe here the development of an efficient insertional mutagenesis system in Arabidopsis that permits identification of genes by their patterns of expression during development. Transposable elements of...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.14.1797
更新日期:1995-07-15 00:00:00
abstract::We describe the developmental effects of the expression of a normal and mutated Drosophila ras gene ras2 in transgenic Drosophila. A Gly14----Val14 mutant (Gly14 in ras2 is equivalent to Gly12 in mammalian ras proteins) was constructed in ras2 by site-directed mutagenesis. Inducible constructs of ras2 and ras2Val14 we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.567
更新日期:1988-05-01 00:00:00
abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.18.2266
更新日期:1995-09-15 00:00:00
abstract::The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidire...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1872810
更新日期:2010-01-15 00:00:00
abstract::The myc family of cellular oncogenes encodes three highly related nuclear phosphoproteins (c-Myc, N-Myc, and L-Myc) that are believed to function as sequence-specific transcription factors capable of regulating genes important in cellular growth and differentiation. Current evidence indicates that Myc family proteins ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.8.1480
更新日期:1992-08-01 00:00:00
abstract::Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1661708
更新日期:2008-07-15 00:00:00
abstract::Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.227512.113
更新日期:2013-11-01 00:00:00
abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1270
更新日期:1994-06-01 00:00:00
abstract::The presence of Set2-mediated methylation of H3K36 (K36me) correlates with transcription frequency throughout the yeast genome. K36me targets the Rpd3S complex to deacetylate transcribed regions and suppress cryptic transcription initiation at certain genes. Here, using a genome-wide approach, we report that the Set2-...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1539307
更新日期:2007-06-01 00:00:00
abstract::Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of ci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1194004
更新日期:2004-07-01 00:00:00
abstract::The neurogenic loci of Drosophila are required for proper partitioning of ectodermal cells into epidermal versus neural lineages. The loci appear to encode components of a developmental pathway involving cellular communication. In an effort to understand the role of the neurogenic locus mastermind in these processes, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.10.1688
更新日期:1990-10-01 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
doi:10.1101/gad.285460.116
更新日期:2016-07-01 00:00:00
abstract::De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.231202
更新日期:2002-10-15 00:00:00
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 ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.11.1438
更新日期:1999-06-01 00:00:00
abstract::Establishment of the steroid-producing Leydig cell lineage is an event downstream of Sry that is critical for masculinization of mammalian embryos. Neither the origin of fetal Leydig cell precursors nor the signaling pathway that specifies the Leydig cell lineage is known. Based on the sex-specific expression patterns...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.981202
更新日期:2002-06-01 00:00:00
abstract::The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.23.3639
更新日期:1998-12-01 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
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::Embryonic stem (ES) cells are pluripotent cells with the ability to self-renew indefinitely. These unique properties are controlled by genetic factors and chromatin structure. The exit from the self-renewing state is accompanied by changes in epigenetic chromatin modifications such as an induction in the silencing-ass...
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
abstract::Cellular signaling initiated by Hedgehog binding to Patched1 has profound importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts as a morphogen to specify distinctive cell fates using different concentration thresholds, but our knowledge of how the concentration gradient is interpreted into ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1546307
更新日期:2007-05-15 00:00:00
abstract::Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.823200
更新日期:2000-09-15 00:00:00
abstract::Expression of the Arabidopsis CGS1 gene that codes for cystathionine gamma-synthase is feedback regulated at the step of mRNA stability in response to S-adenosyl-L-methionine (AdoMet). A short stretch of amino acid sequence, called the MTO1 region, encoded by the first exon of CGS1 itself is involved in this regulatio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1317105
更新日期:2005-08-01 00:00:00
abstract::Mediator was resolved from yeast as a multiprotein complex on the basis of its requirement for transcriptional activation in a fully defined system. Three groups of mediator polypeptides could be distinguished: the products of five SRB genes, identified as suppressors of carboxy-terminal domain (CTD)-truncation mutant...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.1.45
更新日期:1998-01-01 00:00:00
abstract::Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.346205
更新日期:2005-09-15 00:00:00
abstract::Protein kinases are key regulators of cellular processes. In spite of considerable effort, a full understanding of the pathways they participate in remains elusive. We globally investigated the proteins that interact with the majority of yeast protein kinases using protein microarrays. Eighty-five kinases were purifie...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1998811
更新日期:2011-04-01 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