Abstract:
:The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2-type, C-terminal zinc finger motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence in culture and in primary retrovirus-induced thymomas. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes. In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in a sequence-specific manner. The Gfi-1 binding site, TAAATCAC(A/T)GCA, was defined via random oligonucleotide selection utilizing a bacterially expressed glutathione S-transferase-Gfi-1 fusion protein. Binding to this site was confirmed by electrophoretic mobility shift assays and DNase I footprinting. Methylation interference analysis and electrophoretic mobility shift assays with mutant oliginucleotides defined the relative importance of specific bases at the consensus binding site. Deletion of individual zinc fingers demonstrated that only zinc fingers 3, 4, and 5 are required for sequence-specific DNA binding. Potential Gfi-1 binding sites were detected in a large number of eukaryotic promoter-enhancers, including the enhancers of several proto-oncogenes and cytokine genes and the enhancer of the human cytomegalovirus (HCMV) major immediate-early promoter, which contains two such sites. HCMV major immediate-early-chloramphenicol acetyltransferase reporter constructs, transfected into NIH 3T3 fibroblasts, were repressed by Gfi-1, and the repression was abrogated by mutation of critical residues in the two Gfi-1 binding sites. These results suggest that Gfi-1 may play a role in HCMV biology and may contribute to oncogenesis and T-cell activation by repressing the expression of genes that inhibit these processes.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Zweidler-Mckay PA,Grimes HL,Flubacher MM,Tsichlis PNdoi
10.1128/mcb.16.8.4024subject
Has Abstractpub_date
1996-08-01 00:00:00pages
4024-34issue
8eissn
0270-7306issn
1098-5549journal_volume
16pub_type
杂志文章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::The establishment of epigenetic marks, such as methylation on histone tails, is mechanistically linked to RNA polymerase II within active genes. To explore the interplay between these modifications in transcribed noncoding as well as coding sequences, we analyzed epigenetic modification and chromatin structure at high...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01684-06
更新日期:2007-02-01 00:00:00
abstract::The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.8.4728
更新日期:1993-08-01 00:00:00
abstract::Human ras genes play central roles in coupling extracellular signals with complex intracellular networks controlling proliferation, differentiation, and apoptosis, among others processes. c-H-ras pre-mRNA can be alternatively processed into two mRNAs due to the inclusion or exclusion of the alternative exon IDX; this ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2927-2941.2003
更新日期:2003-04-01 00:00:00
abstract::The tumor suppressor gene PTEN is a phosphoinositide phosphatase that is inactivated by deletion and/or mutation in diverse human tumors. Wild-type PTEN is expressed both in the cytoplasm and nucleus in normal cells, with a preferential nuclear localization in differentiated or resting cells. To elucidate the relation...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.14.6211-6224.2005
更新日期:2005-07-01 00:00:00
abstract::Two signals activate meiosis in yeast: starvation and expression of the a1 and alpha 2 products of the mating-type locus. Prior studies suggest that these signals stimulate expression of an activator of meiosis, the IME1 (inducer of meiosis) product. We have cloned a gene, IME2, with properties similar to those of IME...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.5.2142
更新日期:1989-05-01 00:00:00
abstract::RAD52 and RAD9 are required for the repair of double-strand breaks (DSBs) induced by physical and chemical DNA-damaging agents in Saccharomyces cerevisiae. Analysis of EcoRI endonuclease expression in vivo revealed that, in contrast to DSBs containing damaged or modified termini, chromosomal DSBs retaining complementa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.4.1891
更新日期:1998-04-01 00:00:00
abstract::During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00508-19
更新日期:2020-04-13 00:00:00
abstract::p27(Kip1) is a member of the Cip-Kip family of cyclin-dependent kinase (Cdk) inhibitors that binds to cyclin-Cdk complexes and inhibits their catalytic activity in response to antiproliferative stimuli. p27(Kip1) is regulated by several posttranscriptional mechanisms, including subcellular localization. We have identi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.15.5631-5642.2000
更新日期:2000-08-01 00:00:00
abstract::Synaptic nuclei of innervated muscle transcribe acetylcholine receptor (AChR) genes at a much higher level than extrasynaptic nuclei. To isolate candidate synaptic regulatory molecules responsible for the unique transcriptional potential of synaptic nuclei, we have taken a subtractive hybridization approach. Here, we ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.11.7095
更新日期:1994-11-01 00:00:00
abstract::Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, g...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.11.4746
更新日期:1989-11-01 00:00:00
abstract::Several eukaryotic transcription factors such as Sp1 or Oct1 contain glutamine-rich domains that mediate transcriptional activation. In human cells, promoter-proximally bound glutamine-rich activation domains activate transcription poorly in the absence of acidic type activators bound at distal enhancers, but synergis...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.8.2774-2782.2000
更新日期:2000-04-01 00:00:00
abstract::Nuclear receptor corepressors (N-CoR) and silencing mediator for retinoid and thyroid receptors (SMRT) have both been implicated in thyroid hormone receptor (TR)-mediated repression. Here we show that endogenous N-CoR, TBL1, and histone deacetylase 3 (HDAC3), but not HDAC1, -2, or -4, are recruited to a stably integra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.15.5122-5131.2003
更新日期:2003-08-01 00:00:00
abstract::Keratin 6 (K6) expression in the epidermis has two components: constitutive expression in the innermost layer of the outer root sheath (ORS) of hair follicles and inducible expression in the interfollicular epidermis in response to stressful stimuli such as wounding. Mice express two K6 isoforms, MK6a and MK6b. To gai...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5248-5255.2000
更新日期:2000-07-01 00:00:00
abstract::Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown. In this study, we investigated the role of a transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), and its isoform...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.5.1971-1979.2005
更新日期:2005-03-01 00:00:00
abstract::P bodies are cytoplasmic RNA granules containing the Dcp1-Dcp2 decapping enzymes where mRNA decay can occur. Here, we describe the characterization of P bodies in the fission yeast Schizosaccharomyces pombe. Most information on the property and function of P bodies stems from studies in the distantly related budding y...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01583-12
更新日期:2013-03-01 00:00:00
abstract::TEL-JAK2 fusion proteins, which are a result of t(9;12)(p24;p13) translocations associated with human leukemia, activate Stat5 in vitro and in vivo and cause a myelo- and lymphoproliferative disease in a murine bone marrow transplant model. We report that Socs-1, a member of the SOCS family of endogenous inhibitors of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.10.3547-3557.2001
更新日期:2001-05-01 00:00:00
abstract::SWI-SNF is an ATP-dependent chromatin remodeling complex that disrupts DNA-histone interactions. Several studies of SWI-SNF activity on mononucleosome substrates have suggested that remodeling leads to novel, accessible nucleosomes which persist in the absence of continuous ATP hydrolysis. In contrast, we have reporte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.9.3058-3068.2000
更新日期:2000-05-01 00:00:00
abstract::The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its protein product p48v-myb is a nuclear, sequence-specific, DNA-binding protein which activates gene expression in transient DNA transfection studies. To investigate the rela...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2591
更新日期:1990-06-01 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::Dominant mutations in the early growth response 2 (Egr2/Krox20) transactivator, a critical regulator of peripheral myelin development, have been associated with peripheral myelinopathies. These dominant mutants interfere with the expression of genes required for myelination by Schwann cells, including that for the mos...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01689-06
更新日期:2007-05-01 00:00:00
abstract::The apoptotic process is accompanied by major changes in chromatin structure and gene expression. The apoptotic genetic program is progressively set up with the inhibition of antiapoptotic genes and the activation of proapoptotic ones. Here, we show that the histone deacetylase 3 (HDAC-3), which is a known co-represso...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00869-06
更新日期:2007-01-01 00:00:00
abstract::An accumulation in cells of unfolded proteins is believed to be the common signal triggering the induction of heat shock proteins (hsps). Accordingly, in Saccharomyces cerevisiae, inhibition of protein breakdown at 30 degrees C with the proteasome inhibitor MG132 caused a coordinate induction of many heat shock protei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.30
更新日期:1998-01-01 00:00:00
abstract::The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.18.8210-8220.2004
更新日期:2004-09-01 00:00:00
abstract::The Son of sevenless proteins (Sos) are guanine nucleotide exchange factors involved in the activation of Ras by cytoplasmic and receptor tyrosine kinases. Growth factor stimulation rapidly induces the phosphorylation of Sos on multiple serine and threonine sites. Previous studies have demonstrated that growth factor-...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.10.5674
更新日期:1996-10-01 00:00:00
abstract::We have developed an in vitro system which faithfully reproduces several aspects of general mRNA stability. Poly(A)- RNAs were rapidly and efficiently degraded in this system with no detectable intermediates by a highly processive 3'-to-5' exonuclease activity. The addition of a poly(A) tail of at least 30 bases, or a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.1.398
更新日期:1997-01-01 00:00:00
abstract::A number of deletion mutants were isolated, including 5', 3', and internal deletions in the 5'-flanking region of the human cellular oncogene related to the Harvey sarcoma virus (c-H-ras), and their transforming activities were examined in NIH 3T3 cells. DNA sequences which could not be detected without losing transfo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2933
更新日期:1987-08-01 00:00:00
abstract::The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.6.3374
更新日期:1991-06-01 00:00:00
abstract::Nuclear expression and consequent biological action of the eukaryotic NF-kappa B transcription factor complex are tightly regulated through its cytoplasmic retention by an ankyrin-rich inhibitory protein termed I kappa B alpha. I kappa B alpha specifically binds to and masks the nuclear localization signal of the RelA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.3.1058
更新日期:1996-03-01 00:00:00
abstract::Nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. Although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (NE) proteins that share a conserved C-terminal SUN (S...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.10.3738-3751.2006
更新日期:2006-05-01 00:00:00