Regulation of TPP 1 (CLN2) Activity

TPP 1 (CLN2) 活动的监管

• 批准号: 7054906
• 负责人: Kevin D. Houston
• 金额: $ 1.72万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-15 至 2006-05-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054906
• 关键词: Dictyostelium; biological signal transduction; cell proliferation; disease /disorder model; endopeptidases; enzyme activity; enzyme mechanism; gene targeting; hexosyltransferase; immunoprecipitation; mass spectrometry; microorganism culture; neuronal ceroid lipofuscinosis; postdoctoral investigator; protein localization; recombinant proteins; serine proteinases; transcription factor; western blottings

DESCRIPTION (provided by applicant): Mutations in the human gene CLN2 cause the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis (LINCL). CLN2 encodes the protease tripeptidyl peptidase I (TPP I). Little is known about the regulation of TPP I and no endogenous substrates have been identified. My preliminary data indicate that in Dictyostelium discoideum TPP I activity is regulated by AprA and AprB, components of a secreted factor that regulates proliferation and development. Genetic evidence indicates that TPP I, an N- acetylglucosaminyltransferase I (DdGNT4), and a protein with similarity to human dentin sialophoshoprotein (DdDSPP) are part of a signal transduction pathway regulated by AprA. I will first determine if AprA and AprB function in the same pathway to regulate TPP I. To test the hypothesis that DdGNT4 is regulated by AprA and AprB downstream of TPP I, DdGNT4 activity will be determined in cells with deficient TPP I activity. To test the hypothesis that DdDSPP is part of the AprA/AprB regulated pathway that regulates TPP I activity, TPP I activity will be measured in cells that lack DdDSPP. Understanding how TPP I functions in a signal transduction pathway may lead to the development of treatments for LINCL.

描述（由申请人提供）：人类基因CLN 2突变导致神经退行性疾病晚期婴儿神经元蜡样质脂褐质沉积症（LINCL）。CLN 2编码蛋白酶三肽基肽酶I（TPP I）。人们对TPP I的调节知之甚少，也没有发现任何内源性底物。我的初步数据表明，在Dictyosteelium discoideum TPP我的活动是由AprA和AprB，一个分泌的因子，调节增殖和发展的组件。遗传证据表明TPP I、N-乙酰葡糖胺转移酶I（DdGNT 4）和一种与人牙本质唾液酸磷蛋白（DdDSPP）相似的蛋白质是AprA调节的信号传导途径的一部分。我将首先确定AprA和AprB是否在相同的途径中调节TPP I。为了检验DdGNT 4受TPP I下游的AprA和AprB调节的假设，将在TPP I活性缺陷的细胞中测定DdGNT 4活性。为了检验DdDSPP是调节TPP I活性的AprA/AprB调节途径的一部分的假设，将在缺乏DdDSPP的细胞中测量TPP I活性。了解TPP I在信号转导途径中的功能可能会导致LINCL治疗的发展。