Abstract:
:A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Howes KA,Ransom N,Papermaster DS,Lasudry JG,Albert DM,Windle JJdoi
10.1101/gad.8.11.1300subject
Has Abstractpub_date
1994-06-01 00:00:00pages
1300-10issue
11eissn
0890-9369issn
1549-5477journal_volume
8pub_type
杂志文章abstract::Transcription by RNA polymerase II (RNAPII) is a dynamic process with frequent variations in the elongation rate. However, the physiological relevance of variations in RNAPII elongation kinetics has remained unclear. Here we show in yeast that a RNAPII mutant that reduces the transcription elongation rate causes wides...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.337212.120
更新日期:2020-07-01 00:00:00
abstract::The WD40 domain-containing protein WRAP53β (WD40 encoding RNA antisense to p53; also referred to as WDR79/TCAB1) controls trafficking of splicing factors and the telomerase enzyme to Cajal bodies, and its functional loss has been linked to carcinogenesis, premature aging, and neurodegeneration. Here, we identify WRAP5...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246546.114
更新日期:2014-12-15 00:00:00
abstract::In the Bar mutation of Drosophila, ommatidial differentiation is known to be suppressed in the anterior portion of the eye. Our structural analysis shows that the Bar region contains a pair of homeo box genes, BarH1 and BarH2. These genes encode polypeptides similar in size and sequence and share a common homeo domain...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.50
更新日期:1992-01-01 00:00:00
abstract::In vivo experiments have demonstrated that the ribosomal protein L32 of Saccharomyces cerevisiae brings about the inhibition of splicing of the transcript of its own gene through an RNA structure comprised largely of the first exon. We now show that L32, itself, binds specifically to this RNA. Splicing of the RPL32 tr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.2.211
更新日期:1994-01-01 00:00:00
abstract::The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.12a.2456
更新日期:1993-12-01 00:00:00
abstract::Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.2.167
更新日期:1997-01-15 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
abstract::Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.391106
更新日期:2006-11-01 00:00:00
abstract::Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer). Because these growth factors are structurally very different, they presumably act through distinct cell surface receptors that i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3038
更新日期:1995-12-15 00:00:00
abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.297135.117
更新日期:2017-05-15 00:00:00
abstract::At least half of all human pre-mRNAs are subject to alternative 3' processing that may modulate both the coding capacity of the message and the array of post-transcriptional regulatory elements embedded within the 3' UTR. Vertebrate poly(A) site selection appears to rely primarily on the binding of CPSF to an A(A/U)UA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1298605
更新日期:2005-06-01 00:00:00
abstract::Commitment to mitosis is regulated by a protein kinase complex called MPF. MPF is inhibited by Wee1-related kinases and activated by Cdc25 phosphatase. MPF activation further boosts Cdc25 and represses Wee1. This feedback control probably involves polo kinase. A dominant cut12.s11 mutation in the Schizosaccharomyces p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256003
更新日期:2003-06-15 00:00:00
abstract::Sexual identity in Drosophila is determined by zygotic X-chromosome dose. Two potent indicators of X-chromosome dose are sisterless-a (sis-a) and sisterless-b (sis-b). Genetic analysis has shown that a diplo-X dose of these genes activates their regulatory target, the feminizing switch gene Sex-lethal (Sxl), whereas a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.9.1688
更新日期:1993-09-01 00:00:00
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...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1748409
更新日期:2009-04-01 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
更新日期:1996-07-15 00:00:00
abstract::In meiosis I, homologous chromosomes pair and then attach to the spindle so that the homologs can be pulled apart at anaphase I. The segregation of homologs before pairing would be catastrophic. We describe two mechanisms that prevent this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian Auro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.227454.113
更新日期:2013-10-01 00:00:00
abstract::Morphogen gradients of secreted molecules play critical roles in the establishment of the spatial pattern of gene expression. During midgut development in Drosophila, secreted molecules of Decapentaplegic (Dpp) and Wingless (Wg) establish unique transcriptional regulation within target cells to specify the resultant c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.17.2724
更新日期:1998-09-01 00:00:00
abstract::The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At pr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.3.289
更新日期:1996-02-01 00:00:00
abstract::Genetic analysis in Arabidopsis has led to the identification of several genes that are required for auxin response. One of these genes, AXR1, encodes a protein related to yeast Aos1p, a protein that functions to activate the ubiquitin-related protein Smt3p. Here we report the identification of a new gene called TRANS...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.2.198
更新日期:1998-01-15 00:00:00
abstract::While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of mi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.303537.117
更新日期:2017-07-15 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::To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development in Saccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast geno...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1389306
更新日期:2006-02-15 00:00:00
abstract::In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.251470.114
更新日期:2015-04-15 00:00:00
abstract::The embryonic ectoderm in Drosophila displays a highly organized arrangement of specific structures along the dorsal-ventral axis. To establish this characteristic design, cells must receive instructive cues regarding their position. We present evidence that during stages 8-9 of embryonic development, the Drosophila E...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.10.1937
更新日期:1993-10-01 00:00:00
abstract::Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.326488.119
更新日期:2019-07-01 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
abstract::Faithful inheritance of genetic information requires that DNA be copied only once each cell cycle. Initiation of DNA replication involves the establishment of a prereplication complex (pre-RC) and subsequent activation by CDK/cyclins, converting the pre-RC to a post-RC. The origin recognition complex (ORC), Cdc6p, and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.24.3375
更新日期:1997-12-15 00:00:00
abstract::A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains....
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::Noncoding RNA regulators have been implicated in almost all imaginable cellular processes. Here we review how regulatory small RNAs such as Spot42, SgrS, GlmY, and GlmZ and a cis-encoded ribozyme in glmS mRNA control sugar metabolism. Besides discussing the physiological implications, we show how the study of these mo...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1717808
更新日期:2008-11-01 00:00:00
abstract::We have identified protein kinase C-zeta (PKC-zeta) as a novel suppressor of neoplastic transformation caused by the v-raf oncogene. PKC-zeta overexpression drastically retards proliferation, abolishes anchorage-independent growth, and reverts the morphological transformation of v-raf-transformed NIH-3T3 cells. The mo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.12.1455
更新日期:1996-06-15 00:00:00