Smyth Peter, Sasiwachirangkul Jutharat, Williams Rich, Scott Christopher J
The Patrick G Johnston Centre for Cancer Research, Queen's University, 97 Lisburn Road, Belfast, BT9 7AE, UK.
The Patrick G Johnston Centre for Cancer Research, Queen's University, 97 Lisburn Road, Belfast, BT9 7AE, UK.
Mol Aspects Med. 2022 Dec;88:101106. doi: 10.1016/j.mam.2022.101106. Epub 2022 Jul 19.
Amongst the lysosomal cysteine cathepsin family of proteases, cathepsin S (CTSS) holds particular interest due to distinctive properties including a normal restricted expression profile, inducible upregulation and activity at a broad pH range. Consequently, while CTSS is well-established as a member of the proteolytic cocktail within the lysosome, degrading unwanted and damaged proteins, it has increasingly been shown to mediate a number of distinct, more selective roles including antigen processing and antigen presentation, and cleavage of substrates both intra and extracellularly. Increasingly, aberrant CTSS expression has been demonstrated in a variety of conditions and disease states, marking it out as both a biomarker and potential therapeutic target. This review seeks to contextualise CTSS within the cysteine cathepsin family before providing an overview of the broad range of pathologies in which roles for CTSS have been identified. Additionally, current clinical progress towards specific inhibitors is detailed, updating the position of the field in exploiting this most unique of proteases.
在溶酶体半胱氨酸组织蛋白酶家族的蛋白酶中，组织蛋白酶S（CTSS）因其独特的特性而备受关注，这些特性包括正常情况下受限的表达谱、可诱导的上调以及在较宽pH范围内的活性。因此，虽然CTSS作为溶酶体内蛋白水解混合物的一员已被充分确立，负责降解不需要的和受损的蛋白质，但越来越多的研究表明它还介导了许多不同的、更具选择性的作用，包括抗原加工和抗原呈递，以及在细胞内和细胞外对底物的切割。越来越多的研究表明，在多种疾病状态下CTSS表达异常，这使其成为一种生物标志物和潜在的治疗靶点。本综述旨在将CTSS置于半胱氨酸组织蛋白酶家族的背景下，然后概述已确定CTSS发挥作用的广泛病理情况。此外，还详细介绍了目前针对特异性抑制剂的临床进展，更新了该领域在利用这种极其独特的蛋白酶方面的进展情况。
