Identification of tubulins as substrates of serine protease HtrA1 by mixture-based oriented peptide library screening.
Identification of tubulins as substrates of serine protease HtrA1 by mixture-based oriented peptide library screening.
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DOI：
10.1002/jcb.22121
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发表时间：
2009-05-15
影响因子：
4
通讯作者：
Shridhar, Viji
中科院分区：
文献类型：
--
作者：
Chien, Jeremy;He, Xiaoping;Shridhar, Viji
丝氨酸蛋白酶HtrA 1属于胰凝乳蛋白酶样蛋白酶家族，首先在细菌中发现，后来在哺乳动物系统中发现。这些蛋白酶被鉴定为原核系统中蛋白质质量控制的组分和哺乳动物系统中多种信号通路的调节剂。特别是，HtrA 1与滋养层细胞迁移和侵袭、肿瘤进展、化疗诱导的细胞毒性、骨关节炎、年龄相关性黄斑变性和阿尔茨海默病的发病机制有关。然而，其在生物系统中的潜在底物的系统分析仍然缺乏。因此，我们进行了基于混合物的定向肽库筛选以鉴定HtrA 1的推定底物。我们鉴定了[AEGR]-[LAGR]-[IAMLR]-[TVIAL]作为P1至P4位点的共有残基。我们确定了几个假定的底物HtrA 1参与各种疾病的发病机制。在这项研究中，我们报告的鉴定微管蛋白作为潜在的底物的HtrA 1，并验证微管蛋白作为体外和细胞内底物的HtrA 1。这些结果为HtrA 1在各种疾病发病机制中的底物鉴定和功能表征提供了初步见解。
Serine protease HtrA1 belongs to a family of chymotrypsin-like proteases that were first identified in bacteria and later in mammalian systems. These proteases were identified as components of protein quality control in prokaryotic systems and as regulators of diverse signaling pathways in mammalian systems. In particular, HtrA1 is implicated in trophoblast cell migration and invasion, tumor progression, chemotherapy-induced cytotoxicity, osteoarthritis, age-related macular degeneration, and pathogenesis of Alzheimer’s disease. However, systematic analysis of its potential substrates in biological system is still lacking. Therefore, we performed a mixture-based oriented peptide library screening to identify putative substrates of HtrA1. We identified [AEGR]-[LAGR]-[IAMLR]-[TVIAL] as consensus residues for P1 to P4 sites. We identified several putative substrates of HtrA1 involved in the pathogenesis of various diseases. In this study, we report on the identification of tubulins as potential substrates of HtrA1, and validated tubulins as in vitro and intracellular substrates of HtrA1. These results provide initial insights into substrate identification and functional characterization of HtrA1 in pathogenesis of various diseases.
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影响因子：
4.8
作者：
Adrain, C;Duriez, PJ;Martin, SJ
通讯作者：
Martin, SJ
影响因子：
4.8
作者：
Hu, SI;Carozza, M;Crowl, RM
通讯作者：
Crowl, RM
影响因子：
4
作者：
Clawson, Gary A.;Bui, Vuong;Pan, Weihua
通讯作者：
Pan, Weihua
影响因子：
4.1
作者：
Nie, GY;Hampton, A;Salamonsen, LA
通讯作者：
Salamonsen, LA
DOI：
10.1038/nsb795
发表时间：
2002-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Li, WY;Srinivasula, SM;Shi, YG
通讯作者：
Shi, YG