Genetic Analysis of Polarity
极性的遗传分析
基本信息
- 批准号:7923957
- 负责人:
- 金额:$ 38.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1983
- 资助国家:美国
- 起止时间:1983-08-01 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:6q27AdultAllelesAmino Acid SequenceApoptosisB-Cell LymphomasBlast CellBloodBlood CellsBlood specimenBone MarrowBone Marrow CellsCancer cell lineCell Cycle RegulationCell ProliferationCellsChromosomesClinicalCytoplasmDevelopmentDrosophila genusEmbryoEmbryonic DevelopmentFigs - dietaryGene ProteinsGenesGeneticGrowthGrowth and Development functionHematologic NeoplasmsHematopoiesisHematopoietic NeoplasmsHemocytesHumanHuman Cell LineHyperplasiaImmune responseIn Situ HybridizationLeukemic CellLinkLymphocyteLymphomaMalignant - descriptorMalignant NeoplasmsMammalian CellModelingMutationNatureOncogenesOncogenicOrganOrganismOrthologous GeneOvaryParasitesPathway interactionsPatientsPhenotypePlayProcessProtein IsoformsProteinsRegulationReverse Transcriptase Polymerase Chain ReactionRoleSamplingSignal TransductionSiteSpecificityStagingStem cellsSystemTestingTissuesTranscriptVariantVertebratesabstractingbasebone marrow hyperplasiaclinical remissionflygain of functiongenetic analysisgland developmenthuman tissueimaginal discleukemialoss of functionlymph nodesmalignant lymphocytemutantoverexpressionprogenitorprotein functionresearch studytumorigenesis
项目摘要
Abstract:
The developmental mechanisms of human and Drosophila blood systems show
remarkable parallels. Most genes essential for the formation and maturation of
Drosophila hemocytes are conserved in humans, and the majority is associated with
hematopoietic malignancies.
We have identified a new gene, zfrp8, controlling cell proliferation of the
hematopoietic organs, the lymph glands. Several loss-of-function alleles in zfrp8 cause
enormous hyperplasia of the lymph glands, over-proliferation of immature blood cells,
and severe growth delay in other tissues.
Zfrp8 and its human ortholog, PDCD2, are >50% homologous. PDCD2 appears
to be involved in human blood malignancies. This conclusion is based on its regulation
by the BCL6 (B-cell lymphoma 6) oncogene and its chromosomal localization to a region
of chromosome 6q27, frequently deleted in human lymphomas. In some lymphomas,
PDCD2 is present in the cytoplasm of normal lymphocytes, but is not detected in
malignant lymphocytes, indicating that the gene may have similar function in cell
proliferation in Drosophila and humans.
In the bone marrow and blood of leukemia patients, we have detected high levels
of a smaller form of PDCD2, PDCD2Δ33, barely detected in samples from healthy
controls. High levels of PDCD2Δ33 are also found in all the cancer cell lines we have
tested and thus correlates with increased levels of cell proliferation and oncogenesis.
Because of the Drosophila PDCD2/zfrp8 loss-of-function phenotype, strong hyperplasia
of hemocytes, and the high level of expression of PDCD2Δ33 in malignant tissues, we
propose that high levels of PDCD2Δ33 have an oncogenic effect.
Our experiments are aimed at studying normal lymphgland development. In
particular we are investigating the presence of hematopoietic stem cells and their
differentiation potential. We are also determining the function of zfrp8 in normal lymph
gland development and characterizing the GATA factor pannier that genetically interacts
with zfrp8. We also propose to define the gene products of PDCD2 in vertebrates.
摘要:
人类和果蝇血液系统的发育机制表明,
惊人的相似大多数基因的形成和成熟所必需的
果蝇血细胞在人类中是保守的,并且大多数与
造血系统恶性肿瘤
我们已经发现了一个新的基因,zfrp8,控制细胞增殖,
造血器官淋巴腺zfrp8中的几个功能丧失等位基因导致
淋巴腺大量增生,未成熟血细胞过度增殖,
以及其他组织的严重生长延迟。
Zfrp8和它的人类直系同源物PDCD2具有> 50%的同源性。PDCD2出现
与人类血液恶性肿瘤有关这一结论是基于其监管
通过BCL 6(B细胞淋巴瘤6)癌基因及其染色体定位到一个区域
染色体6q27,经常在人类淋巴瘤中缺失。在一些淋巴瘤中,
PDCD2存在于正常淋巴细胞的细胞质中,但在正常淋巴细胞中未检测到。
提示该基因在恶性淋巴细胞中可能具有类似的功能
在果蝇和人类中的增殖。
在白血病患者的骨髓和血液中,我们检测到高水平的
一种较小形式的PDCD2,PDCD2 Δ 33,在健康人的样本中几乎没有检测到。
对照高水平的PDCD2 Δ 33也发现在所有的癌细胞系中,
测试,因此与细胞增殖和肿瘤发生水平的增加相关。
由于果蝇PDCD2/zfrp8功能丧失表型,
和PDCD2 Δ 33在恶性组织中的高水平表达,我们
提出高水平的PDCD2 Δ 33具有致癌作用。
我们的实验旨在研究正常淋巴腺的发育。在
特别是我们正在研究造血干细胞的存在及其
分化潜能我们也在确定zfrp8在正常淋巴中的功能。
腺体发育和表征遗传相互作用的加塔因子pannier
ZFRP 8我们还建议定义脊椎动物中PDCD 2的基因产物。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.
组蛋白H4赖氨酸20的异常单甲基化激活了果蝇中的DNA损伤检查点。
- DOI:10.1083/jcb.200607178
- 发表时间:2007-01-15
- 期刊:
- 影响因子:7.8
- 作者:Sakaguchi, Ayako;Steward, Ruth
- 通讯作者:Steward, Ruth
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{{ truncateString('Ruth M STEWARD', 18)}}的其他基金
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