Hachmann Janna, Edgington-Mitchell Laura E, Poreba Marcin, Sanman Laura E, Drag Marcin, Bogyo Matthew, Salvesen Guy S
Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA; Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Cancer Biology Program, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford School of Medicine, Stanford, CA 94305, USA.
Chem Biol. 2015 Jan 22;22(1):139-47. doi: 10.1016/j.chembiol.2014.11.011. Epub 2014 Dec 31.
The human paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) plays a central role in nuclear factor-κB (NF-κB) signaling as both a protease and scaffolding protein. Knocking out MALT1 leads to impaired NF-κB signaling and failure to mount an effective immune response. However, it is unclear to which degree it is the scaffolding function versus the proteolytic activity of MALT1 that is essential. Previous work involving a MALT1 inhibitor with low selectivity suggests that the enzymatic function plays an important role in different cell lines. To help elucidate this proteolytic role of MALT1, we have designed activity-based probes that inhibit its proteolytic activity. The probes selectively label active enzyme and can be used to inhibit MALT1 and trace its activity profile, helping to create a better picture of the significance of the proteolytic function of MALT1.
人类副胱天蛋白酶黏膜相关淋巴组织淋巴瘤易位蛋白1（MALT1）作为一种蛋白酶和支架蛋白，在核因子κB（NF-κB）信号传导中发挥核心作用。敲除MALT1会导致NF-κB信号传导受损，无法产生有效的免疫反应。然而，尚不清楚MALT1的支架功能与蛋白水解活性在何种程度上是必不可少的。先前涉及低选择性MALT1抑制剂的研究表明，酶功能在不同细胞系中起重要作用。为了帮助阐明MALT1的这种蛋白水解作用，我们设计了基于活性的探针来抑制其蛋白水解活性。这些探针可选择性标记活性酶，可用于抑制MALT1并追踪其活性谱，有助于更清楚地了解MALT1蛋白水解功能的重要性。
