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GENE REGULATION OF RAT DENTIN SIALOPROTEIN

GENE REGULATION OF RAT DENTIN SIALOPROTEIN
大鼠牙本质唾液酸蛋白的基因调控
批准号:
2132760
负责人:
HELENA H Ritchie
金额:
$1.61万
依托单位国家:
美国
项目类别:
财政年份:
1995
资助国家:
美国
项目状态:
已结题
起止时间:
1995-09-30 至 1996-01-31

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中文摘要
翻译
尽管牙本质形成的机制尚不清楚,但它是 一组独特的细胞外基质(ECM)蛋白 参与前牙本质的形成及其后续的 矿化形成牙本质。成熟的成牙本质细胞分泌胶原蛋白 矿化过程中的细胞边界和非胶原蛋白 前方(可能通过成牙本质细胞过程)。以下是NCPs表格 与胶原蛋白形成复合体。形成了碳酸盐磷灰石晶体,这 晶体起始和生长的特定部位过程被认为是 受胶原-NCP复合体控制。为了澄清细节 关于牙本质发生的信息,与NCP相关的附加信息,他们的 新陈代谢和基因调控是必要的。特别值得关注的是 牙本质细胞外基质中所特有的蛋白质。一种牙本质特有的蛋白质, 牙本质唾液酸蛋白是一种53 kDa的富含唾液酸的蛋白质 在整体性质上与细胞附着蛋白骨骼相似的蛋白质 唾液蛋白(BSP)和骨桥蛋白(OPN)。然而,数字信号处理器是人工合成的 只能通过成牙本质细胞和牙髓,不能通过成骨细胞或其他细胞 类型。由其cDNA推导出的DSPDNA序列与 BSP、OPN和其他蛋白质的结合。DSP包含N-的通用序列 和O-糖基化位点,以及酪蛋白激酶和11 磷酸化位点。Northern blotts检测到多个转录本 大约4.6 kb和1.5 kb。基因组的最新Southern杂交分析 克隆强烈提示存在两个相关的数字信号处理器基因。 我们推测,DSP的合成和分泌对 形成健康的牙本质。为了检验这一假设,我们将 利用分子生物学技术阐明基因结构和 他们的规定。我们提出了以下具体目标:一、确定 数字信号处理器基因的基因组组织(S)。2.刻画多个 DSP转录并检测其空间和时间表达 这些文字记录。3.数字信号处理器基因启动子S(S)的特征 包括DNA序列、最小调控序列和核 转录因子和4.研究数字信号处理器的电位调节 基因(S)通过信号转导分子。这篇文章中概述的研究 该提案将为理解重要的 控制牙本质形成的调控事件。
英文摘要
Although the mechanisms involved in dentinogenesis are unknown, it is clear that a unique set of extracellular matrix (ECM) proteins participates in the formation of predentin and its subsequent mineralization to form dentin. Mature odontoblasts secrete collagen at the cell border and non-collagenous proteins (NCPs) at the mineralization front (possibly through odontoblastic processes). Here NCPs form complexes with collagen. Carbonate apatite crystals are formed and this site-specific process of crystal initiation and growth is believed to be controlled by the collagen-NCP complex. In order to elucidate details of dentinogenesis, additional information relative to the NCPs, their metabolism and gene regulation is needed. Of particular interest are proteins found uniquely in dentin ECM. One dentin specific protein, dentin sialoprotein (DSP), a 53 kDa protein, is a sialic acid-rich protein similar in overall properties to cell attachment proteins bone sialoprotein (BSP) and osteopontin (OPN). However, DSP is synthesized only by odontoblasts and dental pulp and not by osteoblasts or other cell types. The sequence of DSP deduced from its cDNA is dissimilar to those of BSP, OPN and other proteins. DSP contains consensus sequences for N- and O-glycosylation sites, as well as casein kinase and 11 phosphorylation sites. Northern blots detected multiple transcripts of approximately 4.6 kb and 1.5 kb. Recent Southern blot analysis of genomic clones strongly suggests the presence of two related DSP genes. We hypothesize that the synthesis and secretion of DSP is crucial to the formation of healthy dentin. In order to test this hypothesis, we will employ molecular biological techniques to elucidate gene structures and their regulation. We propose the following Specific Aims: i. To determine the genomic organization of DSP gene(s). 2. To characterize multiple DSP transcripts and to examine the spatial and temporal expression of these transcripts. 3. To characterize the promoter(s) of DSP gene(s) including DNA sequence, minimal regulatory sequences and nuclear transcription factors and 4. To study the potential regulation of the DSP gene(s) by signal transducing molecules. The studies outlined in this proposal will provide a solid molecular basis for understanding important regulatory events controlling dentinogenesis.
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