Targeting the Deubiquitinase STAMBPL1 Triggers Apoptosis in Prostate Cancer Cells by Promoting XIAP Degradation.

08:00 EDT 17th April 2019 | BioPortfolio

Summary of "Targeting the Deubiquitinase STAMBPL1 Triggers Apoptosis in Prostate Cancer Cells by Promoting XIAP Degradation."

The zinc metalloprotease STAM-binding protein-like 1 (STAMBPL1) has been identified as a deubiquitinase by specifically cleaving Lys-63-linked polyubiquitin chains, but its cellular function remains unclear. Here we described the potential role of STAMBPL1 in suppression of the intrinsic apoptosis. We observed substantially high amounts of STAMBPL1 proteins in androgen-independent prostate cancer PC3 and DU145 cell lines. STAMBPL1 RNAi depletion triggered caspase-3/-7-dependent apoptosis in PC3 and DU145 cells. STAMBPL1 knockdown-induced apoptosis was accompanied by accumulation of cellular ROS and a decrease in endogenous caspase inhibitor XIAP protein content. Treatment cells with antioxidant NAC delayed STAMBPL1 silencing-induced apoptosis, whereas ectopic expression of XIAP almost completely abrogated apoptosis. We further elucidated that STAMBPL1 knockdown diverted XIAP protein to lysosomal degradation pathway. Taken together, these studies show that STAMBPL1 depletion induces apoptosis by promoting XIAP lysosomal degradation, and suggest that targeting deubiquitinase STAMBPL1 might offer promising therapeutic strategy for prostate cancer.


Journal Details

This article was published in the following journal.

Name: Cancer letters
ISSN: 1872-7980


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Medical and Biotech [MESH] Definitions

A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.

A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.

A forkhead box transcription factor and transcriptional activator which triggers type 1 programmed cell death (APOPTOSIS) in the absence of APOPTOSIS INHIBITING PROTEINS, including neuronal cell death induced by OXIDATIVE STRESS. It recognizes and binds to the DNA sequence 5'-(AG)TAAA(TC)A-3' and also functions in post-transcriptional regulation of the c-MYC PROTO-ONCOGENE.

Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).

Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.

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