The quest for substrates and binding partners: A critical barrier for understanding the role of ADAMTS proteases in musculoskeletal development and disease.
The quest for substrates and binding partners: A critical barrier for understanding the role of ADAMTS proteases in musculoskeletal development and disease.
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DOI：
10.1002/dvdy.248
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Hubmacher D
中科院分区：
文献类型：
--
作者：
Satz-Jacobowitz B;Hubmacher D
分泌的ADAMTS金属蛋白酶参与全身结缔组织的雕刻、重塑和侵蚀，包括肌肉骨骼系统。ADAMTS蛋白酶促进肌肉骨骼发育，病理组织破坏，并在先天性肌肉骨骼疾病中发生突变。例如，ADAMTS9导致肢体发育过程中指间网络退化所需的versican裂解，adamts5介导的骨关节炎聚集蛋白降解导致关节侵蚀，ADAMTS10或ADAMTS17突变导致weil - marchesani综合征，一种伴有骨、关节、肌肉、心脏和眼睛受累的矮小综合征。由于ADAMTS蛋白酶和一般蛋白酶的功能主要由其各自底物的蛋白水解的分子结果决定，因此确定每个ADAMTS蛋白酶的所有生理底物是至关重要的。在这里，我们回顾了目前对ADAMTS蛋白酶及其在肌肉骨骼发育和疾病中的作用的了解，重点介绍了一些已知的生理底物和底物切割的后果。我们进一步强调了鉴定和验证新型ADAMTS底物和结合伙伴的迫切需要，描述了基于质谱的方法的原理，并强调了需要考虑的策略，以验证ADAMTS介导的新型推定底物的蛋白质水解的生理相关性。
Secreted ADAMTS metalloproteases are involved in the sculpting, remodeling, and erosion of connective tissues throughout the body, including in the musculoskeletal system. ADAMTS proteases contribute to musculoskeletal development, pathological tissue destruction, and are mutated in congenital musculoskeletal disorders. Examples include versican cleavage by ADAMTS9 which is required for interdigital web regression during limb development, ADAMTS5-mediated aggrecan degradation in osteoarthritis resulting in joint erosion, and mutations in ADAMTS10 or ADAMTS17 that cause Weill-Marchesani syndrome, a short stature syndrome with bone, joint, muscle, cardiac, and eye involvement. Since the function of ADAMTS proteases and proteases in general is primarily defined by the molecular consequences of proteolysis of their respective substrates, it is paramount to identify all physiological substrates for each individual ADAMTS protease. Here, we review the current knowledge of ADAMTS proteases and their involvement in musculoskeletal development and disease, focusing on some of their known physiological substrates and the consequences of substrate cleavage. We further emphasize the critical need for the identification and validation of novel ADAMTS substrates and binding partners by describing the principles of mass spectrometry-based approaches and by emphasizing strategies that need to be considered for validating the physiological relevance for ADAMTS-mediated proteolysis of novel putative substrates.
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影响因子：
4.8
作者：
Abbaszade, I;Liu, RQ;Burn, TC
通讯作者：
Burn, TC
DOI：
10.1007/978-1-4939-9698-8_1
发表时间：
2020-01-01
期刊：
ADAMTS PROTEASES: METHODS AND PROTOCOLS
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
9.8
作者：
Dagoneau, N;Benoist-Lasselin, C;Cormier-Daire, V
通讯作者：
Cormier-Daire, V
影响因子：
4.8
作者：
Delhon, Laure;Mahaut, Clementine;Le Goff, Carine
通讯作者：
Le Goff, Carine