Abstract:
:Hypoxia promotes stem cell maintenance and tumor progression, but it remains unclear how it regulates long-term adaptation toward these processes. We reveal a striking downregulation of the hypoxia-inducible histone H3 lysine 9 (H3K9) demethylase JMJD1A as a hallmark of clinical human germ cell-derived tumors, such as seminomas, yolk sac tumors, and embryonal carcinomas. Jmjd1a was not essential for stem cell self-renewal but played a crucial role as a tumor suppressor in opposition to the hypoxia-regulated oncogenic H3K9 methyltransferase G9a. Importantly, loss of Jmjd1a resulted in increased tumor growth, whereas loss of G9a produced smaller tumors. Pharmacological inhibition of G9a also resulted in attenuation of tumor growth, offering a novel therapeutic strategy for germ cell-derived tumors. Finally, Jmjd1a and G9a drive mutually opposing expression of the antiangiogenic factor genes Robo4, Igfbp4, Notch4, and Tfpi accompanied by changes in H3K9 methylation status. Thus, we demonstrate a novel mechanistic link whereby hypoxia-regulated epigenetic changes are instrumental for the control of tumor growth through coordinated dysregulation of antiangiogenic gene expression.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Ueda J,Ho JC,Lee KL,Kitajima S,Yang H,Sun W,Fukuhara N,Zaiden N,Chan SL,Tachibana M,Shinkai Y,Kato H,Poellinger Ldoi
10.1128/MCB.00099-14subject
Has Abstractpub_date
2014-10-01 00:00:00pages
3702-20issue
19eissn
0270-7306issn
1098-5549pii
MCB.00099-14journal_volume
34pub_type
杂志文章abstract::Aberrant glycogen synthase kinase 3beta (GSK-3beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00808-08
更新日期:2008-12-01 00:00:00
abstract::The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF wer...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01716-08
更新日期:2009-05-01 00:00:00
abstract::In yeast there are at least 14 members of the beta-karyopherin protein family that govern the movement of a diverse set of cargoes between the nucleus and cytoplasm. Knowledge of the cargoes carried by each karyopherin and insight into the mechanisms of transport are fundamental to understanding constitutive and regul...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8487-8503.2004
更新日期:2004-10-01 00:00:00
abstract::Rpd3(L) and Rpd3(S) are distinct multisubunit complexes containing the Rpd3 histone deacetylase. Disruption of the GCN5 histone acetyltransferase gene shows a strong synthetic phenotype when combined with either an sds3 mutation affecting only the Rpd3(L) complex or an rco1 mutation affecting only Rpd3(S). However, th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00164-08
更新日期:2008-07-01 00:00:00
abstract::alpha 1-Antitrypsin (AT), the major elastase inhibitor in mammalian serum, is produced primarily in the liver. We have characterized AT gene structure and expression in the mouse species Mus caroli, which expresses high levels of AT in the kidneys as well as in the liver. Analysis of cDNA and genomic clones showed tha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.2.760
更新日期:1990-02-01 00:00:00
abstract::ADAR2 is a double-stranded-RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-selective conversion of adenosine to inosine. Previous studies from our laboratory have demonstrated that ADAR2 can modify its own pre-mRNA to create a proximal 3' splice site containing a noncanonical ade...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.2.480-488.2006
更新日期:2006-01-01 00:00:00
abstract::Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02253-05
更新日期:2006-06-01 00:00:00
abstract::ABFI (ARS-binding protein I) is a yeast protein that binds specific DNA sequences associated with several autonomously replicating sequences (ARSs). ABFI also binds sequences located in promoter regions of some yeast genes, including DED1, an essential gene of unknown function that is transcribed constitutively at a h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.887
更新日期:1990-03-01 00:00:00
abstract::The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) translocation in childhood acute pro-B-cell leukemia, encodes a hybrid protein that contains the paired trans-activation domains of E2A (E12/E47) linked to the basic region/leucine zipper DNA-binding and dimerization domain of hepatic leukemia factor (HLF). To a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.6.3247
更新日期:1995-06-01 00:00:00
abstract::Xenopus laevis oogenesis is characterized by an active transcription which ceases abruptly upon maturation. To survey changes in the characteristics of the transcriptional machinery which might contribute to this transcriptional arrest, the phosphorylation status of the RNA polymerase II largest subunit (RPB1 subunit)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.3.1434
更新日期:1997-03-01 00:00:00
abstract::A cDNA encoding a novel Krüppel-type zinc finger protein, FKLF, was cloned from fetal globin-expressing human fetal erythroid cells. The deduced polypeptide sequence composed of 512 amino acids revealed that, like Sp1 and EKLF, FKLF has three contiguous zinc fingers at the near carboxyl-terminal end. A long amino-term...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3571
更新日期:1999-05-01 00:00:00
abstract::In Saccharomyces cerevisiae, the intracellular concentration of trehalose increases rapidly in response to many environmental stresses, including heat shock. These high trehalose levels have been correlated with tolerance to adverse conditions and led to the model that trehalose functions as a chemical cochaperone. He...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01158-06
更新日期:2007-02-01 00:00:00
abstract::A wide range of xenobiotic compounds are metabolized by cytochrome P450 (CYP) enzymes, and the genes that encode these enzymes are often induced in the presence of such compounds. Here, we show that the nuclear receptor CAR can recognize response elements present in the promoters of xenobiotic-responsive CYP genes, as...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.9.2951-2958.2000
更新日期:2000-05-01 00:00:00
abstract::Repair of chromosomal breaks is essential for cellular viability, but misrepair generates mutations and gross chromosomal rearrangements. We investigated the interrelationship between two homologous-repair pathways, i.e., mutagenic single-strand annealing (SSA) and precise homology-directed repair (HDR). For this, we ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.21.9305-9316.2004
更新日期:2004-11-01 00:00:00
abstract::Regulation of variant surface glycoprotein (VSG) mRNA turnover in Trypanosoma brucei was studied in bloodstream forms, in procyclic cells, and during in vitro transformation of bloodstream forms to procyclic cells by approach-to-equilibrium labeling and pulse-chase experiments. Upon initiation of transformation at 27 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1242
更新日期:1987-03-01 00:00:00
abstract::Phosphorylation is important in p53-mediated DNA damage responses. After UV irradiation, p53 is phosphorylated specifically at murine residue Ser389. Phosphorylation mutant p53.S389A cells and mice show reduced apoptosis and compromised tumor suppression after UV irradiation. We investigated the underlying cellular pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01610-07
更新日期:2008-03-01 00:00:00
abstract::Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FH...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00636-16
更新日期:2017-05-02 00:00:00
abstract::We have constructed an ALDH3a1 null mouse to investigate the role of this enzyme that comprises nearly one-half of the total water-soluble protein in the mouse corneal epithelium. ALDH3a1-deficient mice are viable and fertile, have a corneal epithelium with a water-soluble protein content approximately half that of wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.3.849-855.2002
更新日期:2002-02-01 00:00:00
abstract::Nuclear microinjection of c-H-ras DNA induced DNA synthesis in reversibly nonproliferating quiescent human cells. The proto-oncogene and oncogene forms were equally effective inducers. In contrast, c-H-ras DNA either alone or in combination with the adenovirus E1A gene did not cause terminally nondividing senescent ce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.8.2990
更新日期:1986-08-01 00:00:00
abstract::Transfection of C3H/10T1/2 cells with a c-myc gene resulted in the acquisition of responsiveness to transforming growth factor type beta. Cells transfected with an activated H-ras gene or an H-ras and c-myc gene, however, exhibited a transformed morphology and spontaneous soft-agar growth, a phenotype induced reversib...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2649
更新日期:1987-07-01 00:00:00
abstract::The generation of two daughter cells with the same genetic information requires error-free chromosome segregation during mitosis. Chromosome transmission fidelity is dependent on spindle structure/function, which requires Asp1 in the fission yeast Schizosaccharomyces pombe Asp1 belongs to the diphosphoinositol pentaki...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00047-18
更新日期:2018-04-16 00:00:00
abstract::The full-length normal and T24 mutant human H-ras proteins and two truncated derivatives of the T24 mutant were expressed efficiently in Escherichia coli. The proteins accumulated to 1 to 5% of total cellular protein, and each was specifically recognized by anti-ras monoclonal antibodies. The two full-length proteins ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1015
更新日期:1985-05-01 00:00:00
abstract::In Drosophila and several other metazoan organisms, there are two genes that encode related but distinct homologs of ADA2-type transcriptional adaptors. Here we describe mutations of the two Ada2 genes of Drosophila melanogaster. By using mutant Drosophila lines, which allow the functional study of individual ADA2s, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.18.8215-8227.2005
更新日期:2005-09-01 00:00:00
abstract::Bcl10 is a critical regulator of NF-kappa B activity in T and B cells, coupling antigen receptor signaling to NF-kappa B activation via protein kinase C (PKC). Here we show that PKC or T-cell receptor (TCR)/CD28 signaling results in downregulation of Bcl10 protein levels, thereby attenuating NF-kappa B transcriptional...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.9.3860-3873.2004
更新日期:2004-05-01 00:00:00
abstract::Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore ge...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.14.5235-5247.2002
更新日期:2002-07-01 00:00:00
abstract::We used a transient-expression assay to identify two estrogen response elements (EREs) associated with the major chicken vitellogenin gene (VTGII). Each element was characterized by its ability to confer estrogen responsiveness when cloned in either orientation next to a chimeric reporter gene consisting of the herpes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.3.1123
更新日期:1988-03-01 00:00:00
abstract::Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00665-15
更新日期:2015-12-01 00:00:00
abstract::We have previously identified poly(A)-binding protein 1 (PABP1) as a ligand for paxillin and shown that the paxillin-PABP1 complex undergoes nucleocytoplasmic shuttling. By targeting the paxillin-binding subdomain sequences in PABP1, we have generated mutants of PABP1 that do not bind to cellular paxillin. Here we rep...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3763-3773.2005
更新日期:2005-05-01 00:00:00
abstract::The Ste12p transcription factor controls the expression of Ty1 transposable element insertion mutations and genes whose products are required for mating in Saccharomyces cerevisiae. The binding site for Ste12p is a consensus DNA sequence known as a pheromone response element (PRE). Upstream activating sequences (UASs)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4330
更新日期:1997-08-01 00:00:00
abstract::The ADP/ATP translocator, a transmembrane protein of the mitochondrial inner membrane, is coded in Saccharomyces cerevisiae by the nuclear gene PET9. DNA sequence analysis of the PET9 gene showed that it encoded a protein of 309 amino acids which exhibited a high degree of homology with mitochondrial translocator prot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.626
更新日期:1986-02-01 00:00:00