DROSOPHILA LYSYL OXIDASE-LIKE PROTEINS

果蝇赖氨酰氧化酶样蛋白

基本信息

  • 批准号:
    7381088
  • 负责人:
  • 金额:
    $ 15.84万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-05-01 至 2007-04-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As described in our last report, human lysyl oxidase-like 2 protein (HLOXL2) has been implicated in the metastasis of breast cancer cells and in the deposition of large amounts of collagen fibers. We anticipate therapeutic agents against HLOXL2 will be useful in preventing cancer from spreading and will reduce the recurrence of cancer following surgical removal of breast tumors. In order to develop these drugs, it is important to understand the basic biochemical and physiological functions of HLOXL2 and closely related proteins. To date, few biochemical studies have been reported for HLOXL2. Because it is difficult to work on human proteins (i.e., limited amounts, availability, inability to conduct genetic experiments), we have chosen to work with the fruit fly Drosophila melanogaster proteins. The genome of the fruit fly has two genes (dloxl1 and dloxl2) that encode proteins very similar to HLOXL2. We aim to characterize these fly proteins and use the results to understand the function of human LOXL2 and its role in cancer metastasis. Initially, we determined that the two genes are differentially expressed in different tissue at distinct developmental stages. dloxl1 is expressed robustly in prepupae while dloxl2 is only expressed in adult flies. Tissue specific analyses have been used to demonstrate that the expression of dloxl1 is confined to salivary glands. Surprisingly, we found that dloxl2 was expressed only in adult heads and not in the bodies. To determine the tissue specific expression of dloxl2 in adult heads, we isolated polyA mRNAs from eya2 (eye absent) mutant flies We could not detect dlox2 expression in the eya2 samples, strongly suggesting that dloxl2 is expressed in the eye. We have begun to produce polyclonal antibodies specific for each of the Drosophila LOXL proteins. We have been able to obtain an antibody against a DlOXL2 peptide in the LOX core domain. The antibody recognizes a ~52 kDa band from bacteria that express a GST-tagged DLOXL2 LOX core domain but not from bacteria expressing a similar GST fusion protein from DLOXL1. We are currently testing the antisera on blots of Drosophila tissues. In addition, we are in the process of generating antibodies specific for DLOXL1 using a GST fusion of the entire DLOXL1 coding sequence, because our attempts to use DLOXL1-specific peptides have thus far have not been successful. Our immediate plan is to focus on defining the subcellular localization of DLOXLs by in situ immunostaining, developing loss-of-function-flies that lack DOXL1 to understand the physiological importance of the gene and the biochemical characterization of the native DLOXLs.
该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者(PI)可能从另一个NIH来源获得主要资金,因此可以在其他CRISP条目中表示。所列机构为中心,不一定是研究者所在机构。如我们在上一份报告中所述,人赖氨酰氧化酶样2蛋白(HLOXL 2)与乳腺癌细胞的转移和大量胶原纤维的沉积有关。我们预期针对HLOXL 2的治疗剂将可用于预防癌症扩散,并将减少乳腺肿瘤手术切除后的癌症复发。为了开发这些药物,重要的是要了解HLOXL 2和密切相关的蛋白质的基本生化和生理功能。迄今为止,很少有关于HLOXL 2的生化研究报道。因为很难在人类蛋白质上工作(即,有限的数量,可用性,无法进行遗传实验),我们选择了果蝇蛋白质。果蝇的基因组有两个基因(dloxl 1和dloxl 2),编码与HLOXL 2非常相似的蛋白质。我们的目标是表征这些苍蝇蛋白,并使用结果来了解人类LOXL 2的功能及其在癌症转移中的作用。最初,我们确定这两个基因在不同发育阶段的不同组织中差异表达。dloxL 1在包皮中稳健表达,而dloxL 2仅在成年果蝇中表达。组织特异性分析已被用于证明dloxl 1的表达仅限于唾液腺。令人惊讶的是,我们发现dloxl 2只在成年人的头部表达,而在身体中不表达。为了确定dloxl 2在成年头部中的组织特异性表达,我们从eya 2(眼缺失)突变果蝇中分离了polyA mRNA。我们在eya 2样品中不能检测到dlox 2表达,强烈表明dloxl 2在眼中表达。我们已经开始生产针对每种果蝇LOXL蛋白的多克隆抗体。我们已经能够获得针对LOX核心结构域中的D10 XL 2肽的抗体。该抗体识别来自表达GST标记的DLOXL 2 LOX核心结构域的细菌的约52 kDa条带,但不识别来自表达来自DLOXL 1的类似GST融合蛋白的细菌的约52 kDa条带。我们目前正在果蝇组织的印迹上测试抗血清。此外,我们正在使用整个DLOXL 1编码序列的GST融合物产生对DLOXL 1特异性的抗体,因为我们使用DLOXL 1特异性肽的尝试迄今尚未成功。我们的近期计划是专注于通过原位免疫染色确定DLOXL的亚细胞定位,开发缺乏DOXL 1的功能丧失果蝇,以了解该基因的生理重要性和天然DLOXL的生化特征。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Minae Mure其他文献

Minae Mure的其他文献

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{{ truncateString('Minae Mure', 18)}}的其他基金

Understanding the roles of PTM's in modulating molecular functions of lysyl oxidase-like 2 in breast cancer cells
了解 PTM 在调节乳腺癌细胞赖氨酰氧化酶样 2 分子功能中的作用
  • 批准号:
    8802535
  • 财政年份:
    2014
  • 资助金额:
    $ 15.84万
  • 项目类别:
Understanding the roles of PTM's in modulating molecular functions of lysyl oxidase-like 2 in breast cancer cells
了解 PTM 在调节乳腺癌细胞赖氨酰氧化酶样 2 分子功能中的作用
  • 批准号:
    8931006
  • 财政年份:
    2014
  • 资助金额:
    $ 15.84万
  • 项目类别:
Understanding the roles of PTM's in modulating molecular functions of lysyl oxidase-like 2 in breast cancer cells
了解 PTM 在调节乳腺癌细胞赖氨酰氧化酶样 2 分子功能中的作用
  • 批准号:
    9134843
  • 财政年份:
    2014
  • 资助金额:
    $ 15.84万
  • 项目类别:
Mechanism and inhibition of collagen prolyl-4-hydroxylases
胶原蛋白脯氨酰-4-羟化酶的作用机制及抑制作用
  • 批准号:
    8072106
  • 财政年份:
    2007
  • 资助金额:
    $ 15.84万
  • 项目类别:
Mechanism and inhibition of collagen prolyl-4-hydroxylases
胶原蛋白脯氨酰-4-羟化酶的作用机制及抑制作用
  • 批准号:
    7407572
  • 财政年份:
    2007
  • 资助金额:
    $ 15.84万
  • 项目类别:
Mechanism and inhibition of collagen prolyl-4-hydroxylases
胶原蛋白脯氨酰-4-羟化酶的作用机制及抑制作用
  • 批准号:
    7614229
  • 财政年份:
    2007
  • 资助金额:
    $ 15.84万
  • 项目类别:
DROSOPHILA LYSYL OXIDASE-LIKE PROTEINS
果蝇赖氨酰氧化酶样蛋白
  • 批准号:
    7609709
  • 财政年份:
    2007
  • 资助金额:
    $ 15.84万
  • 项目类别:
Mechanism and inhibition of collagen prolyl-4-hydroxylases
胶原蛋白脯氨酰-4-羟化酶的作用机制及抑制作用
  • 批准号:
    7808742
  • 财政年份:
    2007
  • 资助金额:
    $ 15.84万
  • 项目类别:
DROSOPHILA LYSYL OXIDASE-LIKE PROTEINS
果蝇赖氨酰氧化酶样蛋白
  • 批准号:
    7170247
  • 财政年份:
    2005
  • 资助金额:
    $ 15.84万
  • 项目类别:

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Lysyl Oxidase在肿瘤转移中的作用机制研究
  • 批准号:
    30971495
  • 批准年份:
    2009
  • 资助金额:
    33.0 万元
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Topical Eyedrops Increasing Lysyl Oxidase Activity to Control Myopia
局部滴眼剂增加赖氨酰氧化酶活性来控制近视
  • 批准号:
    10603432
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    2023
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  • 批准号:
    23K06417
  • 财政年份:
    2023
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Vascular Smooth Muscle Lysyl Oxidase Mediated Increase in Vessel Stiffness and its Effect on Rho-Kinase Mechanosensors
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  • 批准号:
    10768089
  • 财政年份:
    2023
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    $ 15.84万
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赖氨酰氧化酶在动脉粥样硬化中的重要性
  • 批准号:
    10543402
  • 财政年份:
    2022
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    $ 15.84万
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The Multiple Roles of Lysyl Oxidase in Arteriovenous Fistula Failure
赖氨酰氧化酶在动静脉内瘘衰竭中的多重作用
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effect of lysyl oxidase-induced matrix rigidity change on fat browning
赖氨酰氧化酶诱导的基质刚性变化对脂肪褐变的影响
  • 批准号:
    20K08894
  • 财政年份:
    2020
  • 资助金额:
    $ 15.84万
  • 项目类别:
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Lysyl Oxidase Like 2: A Novel Target in Aging Associated Vascular Stiffening
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Lysyl Oxidase Like 2: A Novel Target in Aging Associated Vascular Stiffening
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