Ask about this productRelated genes to: USP36 antibody
- Gene:
- USP36 NIH gene
- Name:
- ubiquitin specific peptidase 36
- Previous symbol:
- -
- Synonyms:
- KIAA1453, FLJ12851
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-04
- Date modifiied:
- 2015-08-26
Related products to: USP36 antibody
Related articles to: USP36 antibody
- Cutaneous melanoma is an aggressive skin cancer characterized by high rates of recurrence and mortality, especially in its advanced stages. Ferroptosis, a distinct form of programmed cell death, has emerged as a promising therapeutic strategy for cancer. Nevertheless, the regulatory mechanisms underlying ferroptosis in melanoma remain poorly defined. In this study, we aimed to elucidate the role of USP36, a deubiquitinating enzyme that removes ubiquitin from substrate proteins, in the ferroptosis of melanoma cells. Using A375 and SK-MEL-28 melanoma cells treated with the ferroptosis inducer erastin, we analyzed USP36 expression and evaluated its functional role through both overexpression and knockdown experiments. Co-immunoprecipitation and ubiquitination assays demonstrated that USP36 stabilizes APEX1 through the cleavage of its K48-linked ubiquitin chains. We further employed USP36-deficient xenograft models to assess tumor growth and ferroptosis sensitivity. Our results indicate that erastin downregulates USP36, whereas overexpression of USP36 suppresses ferroptosis. Importantly, knockdown of APEX1 abolished the anti-ferroptotic effect of USP36. In addition, USP36-deficient tumors exhibited reduced proliferation and enhanced ferroptosis. Collectively, these findings establish USP36 as an oncogene in melanoma that inhibits ferroptosis through stabilization of APEX1. Therefore, targeting the USP36-APEX1 axis may represent a novel therapeutic approach for melanoma treatment. - Source: PubMed
Publication date: 2026/02/06
Zhang LeiZhang YongYin Hongwu - : Lung cancer is a highly lethal disease characterized by a significant mortality rate. Cisplatin, a common drug used for lung cancer treatment, frequently develops resistance over time. Therefore, overcoming cisplatin resistance is crucial in the effective management of lung cancer. The ubiquitin-proteasome system (UPS) serves as a vital regulatory mechanism for maintaining protein homeostasis within cells. Recent studies have shown that manipulating deubiquitinating enzymes (DUBs) can overcome cisplatin resistance. This study aims to investigate the expression levels of DUBs under cisplatin treatment. : Multiplex RT-PCR analysis was performed to identify potential biomarkers by comparing the differential expression patterns of DUBs, and their expression levels were analyzed by RT-qPCR. In addition, their protein expression levels were determined by western blot analysis. The bioinformatics tools including TCGA database and GEPIA website were used to validate potential as prognostic markers in lung cancer. : Multiplex RT-PCR analysis was performed to identify potential biomarkers by comparing the differential expression patterns of DUB genes. Multiplex RT-PCR showed distinct mRNA expression profiles of several DUB genes, including USP35, USP36, USP37, USP47, USP49, and OTUD6B in A549 lung cancer cells following exposure to cisplatin. In addition, RT-qPCR analysis revealed the downregulation of USP35, USP36, USP37, USP47, USP49, and OTUD6B, juxtaposed with the upregulation of USP47 under cisplatin treatment. Substantiating these findings, western blotting analysis confirmed the protein expression levels of USP35, USP36, USP37, USP47, USP49, and OTUD6B in cisplatin-treated lung cancer cells, mirroring the mRNA trends observed in non-treated counterparts except for OTUD6B. Bioinformatics analysis demonstrates that these DUBs except USP47 are upregulated and overall survival analysis indicates that lower expression of these DUBs, except USP37 and USP49, is correlated with improved overall survival in lung cancer patients. : These findings strongly suggest that DUBs may play a crucial role in overcoming cisplatin resistance and improving the treatment efficacy for lung cancer. - Source: PubMed
Publication date: 2026/01/01
Jin Sun-KyuKim Tae-WooChoi Hae-SeulLee Chae-WonBaek Kwang-Hyun - Metabolic reprogramming is a hallmark of clear-cell renal cell carcinoma (ccRCC), driving tumor progression and altering the tumor microenvironment (TME), making it crucial to understand metabolic dysregulation in ccRCC and to identify new therapeutic targets for patients. In this study, metabolomic profiling identified elevated levels of methylmalonic acid (MMA) in ccRCC, attributed to downregulation of methylmalonyl-CoA mutase (MMUT). MMA produced by ccRCC accumulates in the TME and activates the suppressor of fused (SUFU)-regulated Hedgehog signaling pathway in a dose-dependent manner, promoting M2 polarization of macrophages and tumor progression. Mechanistically, MMA induces methylmalonylation at the K499 site of ubiquitin-specific peptidase 36 (USP36), inhibiting USP36-mediated deubiquitination and SUMOylation of SUFU, thereby promoting the expression of GLI family zinc finger 1 (GLI1) and its target genes. Both in vitro and in vivo experiments demonstrated that a low branched-chain amino acids (BCAAs) diet or treatment with the de-methylmalonylation agent MC3138 effectively inhibited M2 polarization of macrophages and tumor progression. These findings emphasize the critical role of MMA in ccRCC pathogenesis and suggest that combining a low-BCAAs diet with MC3138 therapy may offer a promising treatment strategy for ccRCC patients with elevated MMA levels. - Source: PubMed
Publication date: 2025/12/15
Miao DaojiaShi JianTan DiaoyiZhao ChuanyiLv QingyangLu FeiyiYang JunkaiYang HongmeiXiong ZhiyongZhang Xiaoping - Castration-resistant prostate cancer (CRPC) often emerges within a few years following androgen deprivation therapy, and therapeutic options remain limited. Androgen deprivation induces oxidative stress in prostate cancer (PCa) cells, leading to aberrant activation of androgen receptor (AR) signaling. This study aims to clarify the molecular mechanism underlying oxidative stress-induced AR activation in CRPC. Transcriptional activity of the prostate-specific antigen (PSA) promoter was evaluated using a dual-luciferase reporter assay under various treatments. To identify AR-interacting proteins under oxidative stress, TurboID-mediated proximity biotin labeling coupled with mass spectrometry was employed following HO exposure. Protein-protein interactions between AR and ubiquitin-specific peptidase 36 (USP36) were validated by co-immunoprecipitation (Co-IP). Subcellular AR expression was assessed via Immunofluorescence in PCa cells. Low doses HO (10 and 20 μM) enhanced viability and induced oxidative stress in PCa cells, and these concentrations were therefore selected for subsequent experiments. HO treatment activated the AR-PSA signaling axis. The deubiquitinating enzyme USP36 was identified among the proteins that interact with AR upon HO stimulation. Co-IP confirmed the specific binding between AR and USP36. Functional studies revealed that USP36 deubiquitinates and stabilizes AR. Notably, knockdown of USP36 abolished HOinduced activation of the AR-PSA pathway. HO promotes the interaction between USP36 and AR, resulting in AR stabilization, transcriptional activation of PSA, and conferring androgen resistance. These findings provide mechanistic insights into how oxidative stress reactivates AR signaling in PCa and highlight potential therapeutic strategies for different stages of PCa. - Source: PubMed
Publication date: 2025/11/26
Fan ChanghuiHuang ZhihengGao JunfengGu YulongWang NingZhou Bo - DNA double-strand break (DSB) repair via homologous recombination (HR) is critical for maintaining genomic integrity and requires proper DNA end resection to generate single-stranded DNA (ssDNA) overhangs. However, the mechanisms governing this critical step in cells remains poorly understood. Here, we report that GNL3, a nucleolar GTP-binding protein, plays a key role in HR repair via regulating DNA end resection dependently on its SUMOylation. Ectopic expression of wild-type, but not the SUMO-defective K196R mutant, GNL3 completely abolished DNA damage response induced by knockdown of endogenous GNL3. GNL3 interacts with the BLM-DNA2 helicase-nuclease complex and is critical for DNA end resection and subsequent loading of RPA and RAD51. This interaction requires SUMOylation and SUMO-interacting motifs (SIMs) in both proteins. We further demonstrate that USP36, a nucleolar deubiquitinating enzyme, functions as a novel SUMO ligase for GNL3, while the SUMO protease SENP3 deSUMOylates GNL3. Notably, several breast cancer-derived GNL3 variants that disrupt its SUMOylation or SIM fail to interact with the BLM-DNA2 complex. Knockdown of GNL3 sensitizes HR-proficient breast cancer cells to etoposide or Olaparib treatment. Together, our results reveal that GNL3 SUMOylation is crucial for HR repair and suggest that targeting GNL3 SUMOylation may induce HR deficiency, thereby sensitizing breast cancers to DNA damage-inducing agents. - Source: PubMed
Publication date: 2025/11/05
Yang YunhanLi YanpingDai Roselyn SChen CanpingZientek KeithReddy AshokXia ZhengSears Rosalie CSun Xiao-XinDai Mu-Shui