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 specific cytokines (e.g., erythropoietin and interleukin-3) and that activation of the Jak kinase is necessary and sufficient for these effects. Using myleoid cells expressing a series of erythropoietin receptor (EpoR) mutants, we have demonstrated that Jak kinase-dependent signals initiated from the membrane proximal domain of EpoR were sufficient to prevent IR-induced apoptotic cell death, but failed to prevent cell cycle arrest. Cell survival by Epo did not require activation of other known signaling pathways including PI-3 kinase, PLC-gamma, Ras or Stats. Signaling targets of Jak kinase pathways included members of the Bcl-2 family of anti-apoptotic proteins, and enforced expression of Bcl-2 or Bcl-xL was as effective as cytokine treatment in blocking IR-induced apoptosis but did not prevent growth arrest. A distinct signal derived from a membrane distal domain of EpoR is required to overcome growth arrest associated with DNA damage. These findings functionally link the Jak signaling pathway to suppression of p53-mediated cell death by cytokines and demonstrate that the apoptotic and growth arrest responses to DNA damage in hematopoietic cells are modulated by distinct, cytokine specific signal transduction pathways.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Quelle FW,Wang J,Feng J,Wang D,Cleveland JL,Ihle JN,Zambetti GPdoi
10.1101/gad.12.8.1099subject
Has Abstractpub_date
1998-04-15 00:00:00pages
1099-107issue
8eissn
0890-9369issn
1549-5477journal_volume
12pub_type
杂志文章abstract::Previous genetic mosaic studies established that expression of the Drosophila bride of sevenless (boss) gene is required in photoreceptor neuron R8 for the development of photoreceptor neuron R7. This led to the proposal that boss encodes or regulates an R7-specific inductive cue. We have identified the boss gene base...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.11.1835
更新日期:1990-11-01 00:00:00
abstract::We used Sarkosyl to analyze steps along the pathway of transcription initiation by RNA polymerase III. Sarkosyl (0.015%) inhibited transcription when present prior to incubation of RNA polymerase III, TFIIIB, and TFIIIC with the VAI gene, whereas it had no detectable effect on initiation or reinitiation of transcripti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.646
更新日期:1990-04-01 00:00:00
abstract::The ETS transcription factors perform distinct biological functions despite conserving a highly similar DNA-binding domain. One distinguishing property of a subset of ETS proteins is a conserved region of 80 amino acids termed the Pointed (PNT) domain. Using enzyme kinetics we determined that the Ets-1 PNT domain cont...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.950902
更新日期:2002-01-01 00:00:00
abstract::Repression of a-cell specific gene expression in yeast alpha cells requires MAT alpha 2 and MCM1, as well as two global repressors, SSN6 and TUP1. Previous studies demonstrated that nucleosomes positioned adjacent to the alpha 2/MCM1 operator in alpha cells directly contribute to repression. To investigate the possibi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.12.1400
更新日期:1994-06-15 00:00:00
abstract::The timing of asexual fruiting body formation during Aspergillus nidulans colony development is precisely regulated so that conidiophores are typically produced 1-2 mm behind the growing edge of the colony. Mutations in any of four A. nidulans genes, flbB, flbC, flbD, or flbE, result in colonies that are delayed at le...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.4.491
更新日期:1995-02-15 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::Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.1927
更新日期:1992-10-01 00:00:00
abstract::Expression of HNF-4, a transcription factor in the steroid hormone receptor superfamily, is detected only in the visceral endoderm of mouse embryos during gastrulation and is expressed in certain embryonic tissues from 8.5 days of gestation. To examine the role of HNF-4 during embryonic development, we disrupted the g...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.20.2466
更新日期:1994-10-15 00:00:00
abstract::Motor axons make synaptic connections with specific muscles, and this specificity unfolds during development as motoneuron growth cones make specific pathway choices and ultimately recognize and synapse on their specific muscle targets. The Drosophila clueless mutation was identified previously in a genetic screen for...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.23.2936
更新日期:1995-12-01 00:00:00
abstract::In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing. Silencing can be restored in cells lacking Sir proteins by a dominant mutati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.873601
更新日期:2001-04-15 00:00:00
abstract::The transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II. TFIIB possesses sequence-specific DNA-binding ability and interacts with the TFIIB-recognition element (BRE), present in many promoters. Here we show that the BR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.206901
更新日期:2001-11-15 00:00:00
abstract::Coliphage N4 is a double-stranded DNA virus that requires the sequential activity of three different RNA polymerases during infection. The N4 virion RNA polymerase, which is carried in the virion and is injected with the DNA at the start of infection, is responsible for the synthesis of N4 early RNAs. In vitro, the vi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.2010
更新日期:1992-10-01 00:00:00
abstract::Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron-encode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.11.1411
更新日期:1995-06-01 00:00:00
abstract::Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and co...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.269902.115
更新日期:2015-12-15 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
doi:10.1101/gad.2053311
更新日期:2011-05-01 00:00:00
abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.247924.114
更新日期:2015-01-15 00:00:00
abstract::Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.1.64
更新日期:1999-01-01 00:00:00
abstract::The hair follicle undergoes a lifelong developmental cycle that depends on the integration between activating and inhibitory signals acting to regulate and guide the proliferation and differentiation of pluripotent epithelial stem cells. The effectors and mechanisms responsible for re-entry of quiescent telogen hair f...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.223172.113
更新日期:2013-06-15 00:00:00
abstract::Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417607
更新日期:2007-03-15 00:00:00
abstract::The lysosomal storage disorder galactosialidosis results from a primary deficiency of the protective protein/cathepsin A (PPCA), which in turn affects the activities of beta-galactosidase and neuraminidase. Mice homozygous for a null mutation at the PPCA locus present with signs of the disease shortly after birth and ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.21.2623
更新日期:1995-11-01 00:00:00
abstract::A novel 15-kDa protein, RbfA, has been identified by virtue of its ability to act as a high copy suppressor of a previously characterized dominant cold-sensitive mutation (C23U) in 16S rRNA. RbfA is found associated with free 30S ribosomal subunits, but not with 70S ribosomes or polysomes, and is essential for maximal...
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
abstract::Riboswitches are RNA elements that undergo a shift in structure in response to binding of a regulatory molecule. These elements are encoded within the transcript they regulate, and act in cis to control expression of the coding sequence(s) within that transcript; their function is therefore distinct from that of small...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1747308
更新日期:2008-12-15 00:00:00
abstract::Transcriptional profiling is a powerful approach for understanding development and disease. Current cell type-specific RNA purification methods have limitations, including cell dissociation trauma or inability to identify all RNA species. Here, we describe "mouse thiouracil (TU) tagging," a genetic and chemical inters...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.205278.112
更新日期:2013-01-01 00:00:00
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-trans...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1300
更新日期:1994-06-01 00:00:00
abstract::Mammalian telomeres are coated by the sequence-specific, DNA-binding protein, TRF1, a negative regulator of telomere length. Previous results showed that ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. We now show that loss of TRF1 from telomeres results in ubiqui...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1077103
更新日期:2003-06-01 00:00:00
abstract::A cDNA library enriched for transcripts that accumulate from embryonic day 7 until day 1 posthatching was constructed from poly(A)+ RNA of chick optic lobe tissue. From this library, three recombinants were isolated that correspond to neural mRNAs appearing during the major period of synaptogenesis in the retinotectal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.699
更新日期:1987-09-01 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::Drosophila melanogaster neural-specific protein, ELAV, has been shown to regulate the neural-specific splicing of three genes: neuroglian (nrg), erect wing, and armadillo. Alternative splicing of the nrg transcript involves alternative inclusion of a 3'-terminal exon. Here, using a minigene reporter, we show that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.903101
更新日期:2001-10-01 00:00:00
abstract::Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcgammaRIIB. Here we show that upon cross-linking of BCR or BCR with FcgammaRIIB, the rasGAP-associate...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.313270.118
更新日期:2018-07-01 00:00:00