Abstract:
:Hypersensitivity to cross-linking agents and predisposition to malignancy are characteristic of the genetically heterogeneous inherited bone marrow failure syndrome, Fanconi anemia (FA). The protein encoded by the recently cloned FA complementation group A gene, FAA, has been expected to localize in the nucleus as based on the presence of sequences homologous to a bipartite nuclear localization signal (NLS) and a leucine repeat motif. In contrast to this expectation, we show here that a functionally active FAA-green fluorescent protein (GFP) hybrid resides in the cytoplasmic compartment of human kidney 293 cells. In accordance with this finding, disruption of the putative NLS by site-directed mutagenesis failed to affect both subcellular localization and the capacity to complement hypersensitivity to the cross-linking agent mitomycin C in FA-A lymphoblasts. Furthermore, the N-terminal part of FAA with the putative NLS at amino acid position 18 to 35 showed no nuclear translocation activity when fused to GFP, while the first 115 N-terminal amino acids appeared to be indispensable for the complementing activity in FA-A cells. Similarly, mutagenesis studies of the putative leucine repeat showed that, even though this region of the protein is important for complementing activity, this activity does not depend on an intact leucine zipper motif. Finally, fusion of the NLS motif derived from the SV40 large T antigen to FAA could not direct the hybrid protein into the nucleus of 293 cells, suggesting that FAA is somehow maintained in the cytoplasm via currently unknown mechanisms. Thus, like the first identified FA protein, FAC, FAA seems to exert its function in the cytoplasmic compartment suggesting FA proteins to be active in a yet to be elucidated cytoplasmic pathway that governs hematopoiesis and protects against genomic instability.
journal_name
Bloodjournal_title
Bloodauthors
Kruyt FA,Waisfisz Q,Dijkmans LM,Hermsen MA,Youssoufian H,Arwert F,Joenje Hsubject
Has Abstractpub_date
1997-11-01 00:00:00pages
3288-95issue
9eissn
0006-4971issn
1528-0020journal_volume
90pub_type
杂志文章相关文献
BLOOD文献大全abstract::The recent success of chimeric antigen receptor (CAR)-T cell therapy for treatment of hematologic malignancies supports further development of treatments for both liquid and solid tumors. However, expansion of CAR-T cell therapy is limited by the availability of surface antigens specific for the tumor while sparing no...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-08-802926
更新日期:2018-09-13 00:00:00
abstract::In this issue of Blood, Hong et al advocate for use of additional US Food and Drug Administration (FDA)–approved safety measures for transfusion. Most patients transfused with contaminated platelets do not show immediate clinical signs. Active surveillance suggests patient risk 10- to 40-fold higher than passive hemov...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-12-685198
更新日期:2016-01-28 00:00:00
abstract::Forced dimerization or oligomerization has emerged as a powerful mechanism for unleashing the oncogenic properties of chimeric transcription factors in acute leukemias. Fusion of transcriptional regulators with a variety of heterologous partner proteins as a consequence of chromosomal rearrangements induces inappropri...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2004-03-0992
更新日期:2004-08-15 00:00:00
abstract::RUNX1 is crucial for the regulation of megakaryocyte specification, maturation, and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B, respectively, which differ solely in their N-terminal amino acid sequences. ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-06-723635
更新日期:2017-07-20 00:00:00
abstract::In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 p...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1999-08-15 00:00:00
abstract::Targeted disruption of the Friend leukemia integration 1 (Fli-1) proto-oncogene results in severe dysmegakaryopoiesis and embryonic lethality. We used morula-stage aggregation as a strategy to further clarify the hematopoietic defects of the Fli-1 gene-targeted mice. Analyses of lineage expression of Fli-1(+/-) and Fl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-12-4345
更新日期:2005-01-01 00:00:00
abstract::The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-07-15 00:00:00
abstract::Myeloperoxidase (MPO) catalyzes a reaction between chloride and hydrogen peroxide to generate hypochlorous acid and other reactive compounds that have been linked to DNA damage. The MPO gene is expressed at high levels in normal myeloid precursors and in acute myeloid leukemias (AMLs) which are clonal derivatives of m...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::Scurfy mice develop CD4 T-cell-mediated lymphoproliferative disease leading to death within 4 weeks of age. The scurfy mutation causes loss of function of the foxp3 gene (foxp3(sf)), which is essential for development and maintenance of naturally occurring regulatory CD4 T cells (nTregs). In humans, mutations of the f...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-054585
更新日期:2007-08-15 00:00:00
abstract::The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti-beta2-glycoprotein I (beta2GPI) antibodies recognize domain I and cause LAC. The American authors re...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-07-030148
更新日期:2007-02-15 00:00:00
abstract::To understand the regulatory mechanism of erythropoietin (EPO) receptor (EPOR) gene expression, the effect of EPO on the steady-state level of EPOR mRNA was examined using the human EPO-dependent cell line UT-7 as a model system. We found that the treatment of UT-7 cells with EPO resulted in a transient decrease of th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-15 00:00:00
abstract::BMS-354825 (dasatinib) and AMN107 (nilotinib) are potent alternate Abl inhibitors with activity against many imatinib mesylate-resistant BCR-ABL kinase domain (KD) mutants, except T315I. We used N-ethyl-N-nitrosourea (ENU)-exposed Ba/F3-p210(BCR-ABL) cells to compare incidence and types of KD mutants emerging in the p...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-02-004580
更新日期:2006-10-01 00:00:00
abstract::Activation of sialic-acid-binding immunoglobulin-like lectin-G (Siglec-G) by noninfectious damage-associated molecular patterns controls innate immune responses. However, whether it also regulates T-cell-mediated adaptive immune responses is not known. Graft-versus-host reaction is a robust adaptive immune response ca...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-12-545335
更新日期:2014-05-29 00:00:00
abstract::The peripheral blood of acute myeloblastic leukemia (AML) patients often contains large numbers of two distinct cell populations, both capable of forming colonies in culture under similar conditions. The first population consists of the precursors of blast cells and has specificity for AML; the second population consi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1995-05-01 00:00:00
abstract::Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HP...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-07-2705
更新日期:2006-01-15 00:00:00
abstract::The transcription factor nuclear factor-kappaB (NF-kappaB) confers significant survival potential in a variety of tumors. Several established or novel anti-multiple myeloma (anti-MM) agents, such as dexamethasone, thalidomide, and proteasome inhibitors (PS-341), inhibit NF-kappaB activity as part of their diverse acti...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.11.4079
更新日期:2002-06-01 00:00:00
abstract::The putative chemokine receptor BLR1 has been identified as the first G-protein-coupled receptor involved in B-cell migration and in microenvironmental homing to B-cell follicles and to germinal centers. In healthy individuals, expression of BLR1 is restricted to all mature recirculating B cells and to a subpopulation...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-07-15 00:00:00
abstract::Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. B...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2006-06-026104
更新日期:2007-05-01 00:00:00
abstract::In addition to its importance in transfusion, Kell protein is a member of the M13 family of zinc endopeptidases and functions as an endothelin-3-converting enzyme. To obtain information on the structure of Kell protein we built a model based on the crystal structure of the ectodomain of neutral endopeptidase 24.11 (NE...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-05-1564
更新日期:2003-10-15 00:00:00
abstract::The key player for adaptation to reduced oxygen availability is the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of the redox-sensitive HIF-1alpha and the constitutively expressed HIF-1beta subunits. Under normoxic conditions, HIF-1alpha is rapidly degraded, whereas hypoxia, CoCl(2), or desferroxa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.4.1009
更新日期:2001-02-15 00:00:00
abstract::Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene transcription are well understood, very little is known on the signaling events regulating RA-dependent initiation of mRNA translation. We examined whether the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-06-2078
更新日期:2005-02-15 00:00:00
abstract::In this issue of Blood, Mayer et al describe a new method of generating high numbers of Batf3- and Irf8-dependent CD103+ conventional dendritic cells (cDCs), providing new opportunities to study this subset of antigen-presenting cells specialized in crosspresentation. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2014-08-595298
更新日期:2014-11-13 00:00:00
abstract::It was found in a long-term bromodeoxyuridine (BrdU) infusion study that two or more different subpopulations of bone marrow stem cells exist in mice. One of these subpopulations appears to be noncycling and forms approximately 10% of eight-day CFU-S. Another one, a subpopulation of slowly cycling bone marrow cells, i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::In the absence of conclusive assays capable of determining the functionality of ex vivo expanded human hematopoietic progenitor cells, we combined cell tracking with the membrane dye PKH2, immunostaining for CD34, and limiting dilution analysis to estimate the frequency of long-term hematopoietic culture-initiating ce...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-04-15 00:00:00
abstract::In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n = 5317). Subjects were regarded protein S deficient when protein S levels were < 2.5th percentile of the controls. Free and total p...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-04-499335
更新日期:2013-10-31 00:00:00
abstract::The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-11-123844
更新日期:2008-05-01 00:00:00
abstract::Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma (NHL) categorized into endemic, sporadic and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next generation sequenci...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019004099
更新日期:2020-11-10 00:00:00
abstract::Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances numerous functions of mature neutrophils (PMN) including phagocytosis, superoxide responses to chemotaxins, antibody-dependent cellular cytotoxicity, and expression of complement receptors. A central question concerns whether the mechanism of enh...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Inactivation of the retinoblastoma tumor-suppressor gene (RB-1) has been associated with tumorigenicity in various human malignancies. In chronic lymphoid leukemias of B-cell origin (B-CLL) an involvement of RB-1 has been suggested based on cytogenetic data. We examined RB-1 and its chromosomal locus 13q14 in 35 cases...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-04-15 00:00:00