Authors
Seung Un Seo, Seon Min Woo, Yongsoo Kwon, Shin Kim, Hyun-Shik Lee, Sang Hyun Kim, Kyoung-Jin Min, Simmyung Yook, Taeg Kyu Kwon
Published in
Cell death and differentiation. Jun 15, 2026. Epub Jun 15, 2026.
Abstract
Cathepsin L (Cat L), a lysosomal endopeptidase, is overexpressed in human renal clear carcinoma (RCC); however, its impact on apoptosis remains unclear. Results revealed that inhibition (SID, a specific inhibitor), knockdown (siRNA), or knockout of Cat L sensitizes human carcinoma cells to anticancer drugs-mediated apoptosis through the downregulation of Bcl-xL and Survivin at the post-translational level. Moreover, combined treatment with SID and sorafenib reduced the tumor growth in a xenograft model. Deletion of Cat L induced Parkin stabilization by increasing DUB3 expression at the transcriptional level. Parkin knockdown significantly prevented SID-induced Bcl-xL downregulation. Conversely, ectopic expression of Parkin suppressed Bcl-xL expression. Furthermore, SID-mediated Parkin upregulation inhibited USP53 deubiquitinase protein expression, leading to the degradation of Survivin expression through its ubiquitination. Parkin directly ubiquitinated Bcl-xL and USP53, but not Survivin. These results demonstrate that inhibition of Cat L enhances anticancer drugs-induced apoptosis through Parkin-mediated ubiquitination of Bcl-xL and USP53. Moreover, the downregulation of USP53 suppressed the expression of Survivin. Therefore, Cat L can be considered a potential candidate molecular target for the treatment of RCC.
PMID:
42298006
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.
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