泛素化是一种动态可逆的蛋白质翻译后修饰,泛素分子在泛素激活酶、泛素结合酶和泛素连接酶的级联酶促反应催化下共价连接到底物蛋白上。去泛素化酶将泛素分子从底物上移除,动态可逆地调控泛素化修饰,在成熟泛素的生成、泛素链的移除与修剪、游离泛素链的回收等过程中发挥着关键的调控作用。本文的研究对象是酵母中泛素特异性蛋白酶(ubiquitin specific protease,USP)家族成员Ubp14,负责回收细胞内游离的泛素链。本研究定量比较了酵母细胞中Ubp14缺失对全蛋白质组的影响,进而找出其潜在的调控通路和分子功能。首先,通过同源重组技术构建了ubp14△菌株,发现其生长速度低于野生型酵母。利用稳定同位素氨基酸代谢标记技术结合深度覆盖的蛋白质组学分析技术,系统比较了ubp14△菌株相对于野生型菌株的差异蛋白,共计鉴定3685个蛋白,通过统计学分析筛选得到109个差异蛋白。基因本体论分析发现,Ubp14缺失引起的差异蛋白主要参与了包括氨基酸代谢、氧化还原和热应激等生物学过程。本研究为深入探究去泛素化酶Ubp14的生物学功能,进而深刻理解游离泛素的稳态平衡与生物学过程调控提供了高可信的蛋白质组学数据信息。
Objectives Paired box 9(PAX9) is a transcription factor that performs a critical role in the development of human *** various mutations in the PAX9 gene have been identified to date,the mechanisms how these mutations ...
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Objectives Paired box 9(PAX9) is a transcription factor that performs a critical role in the development of human *** various mutations in the PAX9 gene have been identified to date,the mechanisms how these mutations cause non-syndromic tooth agenesis(NSTA) are not completely *** study the pathogenesis of NSTA,a Chinese NSTA family was *** and Methods Genomic DNA was taken from the family ***-exome sequencing were used,followed by Sanger sequencing for *** function of the mutant PAX9 was studied by bioinformatics,real-time PCR,western blotting,Luciferase reporter assay,and *** Here we assess the functional impact of a novel missense PAX9 variant(c.156C>G p.C52W),identified in a Chinese family with NSTA,and provide novel insights into the molecular mechanism of PAX9-C52W *** show that while PAX9-C52W is expressed,even up-regulated,its functionality is severely *** mutation affects the binding affinity between PAX9 and MSX1 and alters transcriptional activity of BMP4 due to mutations like PAX9-C52W can lead to disturbances in the intricate regulatory networks controlling tooth *** molecular changes have significant downstream effects,as evidenced by the decreased capacity of osteo/odontogenic differentiation observed in human dental pulp stem cells(hDPSCs) infected with the PAX9-C52W *** Overall,our studies reveal a dominant-negative effect of the PAX9-C52W against the wild-type PAX9.
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