Novel Nucleus-Oriented Quenched Activity-Based Probes Link Cathepsin Nuclear Localization with Mitosis.

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Tác giả: Galia Blum, Gourab Dey, Tamar Gilon, Emmanuelle Merquiol, Karin Reut Shannon, Boris Turk, Tommy Weiss-Sadan

Ngôn ngữ: eng

Ký hiệu phân loại: 636.0885 Animal husbandry

Thông tin xuất bản: United States : ACS sensors , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 180756

 Cysteine cathepsins are important proteases that are highly upregulated in cancers and other diseases. While their reported location is mostly endolysosomal, some evidence shows their nuclear localization and involvement in the cell cycle. We aim to generate tools to investigate the involvement of cathepsins in the cell cycle progression. To investigate nuclear cathepsin activity, we designed nucleus-directed quenched activity-based probes (qABPs) by attaching cell-penetrating peptides (CPPs). qABPs are active-site-directed compounds that enable direct real-time monitoring of enzyme activity by the covalent linkage between the probe and the enzyme's active site. Biochemical evaluation of the CPP-qABPs showed potent and selective probes
  cell fractionation, multimodal flow cytometry-imaging, and time-lapse movies demonstrated nuclear cathepsin activity in living cells. Interestingly, these probes reveal a spatiotemporal pattern, a surge of nuclear cathepsin just before mitosis, suggesting yet unrevealed roles of cathepsin in cell division. In summary, these nuclear-directed qABPs serve as unique scientific tools to unlock the hidden features of cysteine proteases and to understand their involvement in cell division and cancer.
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