Ask about this productRelated genes to: USP49 antibody
- Gene:
- USP49 NIH gene
- Name:
- ubiquitin specific peptidase 49
- Previous symbol:
- -
- Synonyms:
- MGC20741
- Chromosome:
- 6p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-04
- Date modifiied:
- 2016-10-05
Related products to: USP49 antibody
Related articles to: USP49 antibody
- Bax, a key member of the B-cell lymphoma 2 (Bcl-2) protein family, is essential for inducing mitochondrial apoptosis. In this study, we employed yeast two-hybrid screening to identify ubiquitin-specific protease 49 (USP49) as a binding partner of Bax. Subsequent immunoprecipitation and glutathione S-transferase (GST) pull-down assays confirmed their direct interaction. Functional assays showed that USP49 reduces Bax polyubiquitination at multiple lysine residues within ubiquitin, with the strongest effects observed on K11, K29, K33, and K63 linkages. In contrast, its effect on K48-linked ubiquitination was weak and insufficient to influence Bax protein stability, indicating that USP49 does not regulate Bax abundance through proteasomal degradation. Instead, RT-qPCR analysis revealed that USP49 overexpression significantly increased Bax mRNA levels, and this effect was maintained under apoptosis stimuli (UV, HO, and STS), indicating transcriptional regulation largely independent of stress-induced damage, whereas its effect was modest and not statistically significant under starurosporine treatment. Collectively, these findings demonstrate that USP49 regulates Bax primarily through K29/K33/K63-linked ubiquitination and transcriptional upregulation, highlighting its role as a stress-responsive modulator of apoptosis and a potential therapeutic target in cancer. Moreover, under DNA damage condition (UV), USP49 overexpression marked enhanced apoptosis. - Source: PubMed
Publication date: 2026/05/03
Choi Hae-SeulKim Soo-YeonKim So-RaBaek Kwang-Hyun - Deubiquitinating enzymes (DUBs) are a class of biological macromolecules with molecular weights ranging from 30 to 150 kDa that play extensive roles in tumor initiation and progression. However, their implications in sorafenib resistance in liver cancer remain incompletely understood. In this study, we identified sorafenib resistance-associated DUBs through weighted gene co-expression network analysis and differential expression profiling. Subsequently, we developed a DUB-based predictive model for liver cancer resistance, designated ResiDUBs, using multivariate Cox regression analysis. This model was employed to assess drug resistance and prognostic outcomes. The ResiDUBs model-constructed based on five DUBs (OTUB1, USP32, USP48, USP49, and UBXN1)-stratified patients into high- and low-risk groups. Patients in the high-risk group exhibited significantly greater sorafenib resistance, poorer prognosis, and hyperactivation of the PI3K/AKT signaling pathway. Multi omics analyses, including single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing, consistently identified UBXN1 as the most prominent resistance-associated gene within the ResiDUBs signature. UBXN1 expression was markedly upregulated in treatment-resistant tumors. Knockdown of UBXN1 sensitizes liver cancer cells to sorafenib and inhibits PI3K/AKT pathway activity. Conversely, overexpression of UBXN1 increases cellular resistance to sorafenib, activates the PI3K/AKT pathway, and induces macrophage polarization toward the M2 phenotype. In vivo experiments further demonstrate that UBXN1 knockdown enhances the sensitivity of liver cancer cells to sorafenib and significantly reduces PI3K/AKT pathway activity. Our findings suggest that targeting UBXN1 may represent a promising therapeutic strategy to overcome sorafenib resistance in liver cancer. - Source: PubMed
Publication date: 2026/01/27
Li ManqiXie YuxinWei JinruiWu Lichuan - Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. While ubiquitin-specific peptidase 49 (USP49) has been implicated in various cancers, its role in HCC is unclear. Here, we found that USP49 is upregulated in HCC tissues and associated with poor prognosis. Functional assays demonstrated that USP49 promotes HCC proliferation and migration both in vitro and in vivo. Mechanistically, USP49 directly interacts with and deubiquitinates RACK1, thereby stabilizing it. This stabilization leads to RACK1-driven transcriptional activation of key fatty acid metabolic enzymes, enhancing triglyceride synthesis and fueling tumor growth through metabolic reprogramming. Collectively, our study identifies the USP49/RACK1 axis as a critical driver of HCC progression and nominates USP49 as a promising therapeutic target. - Source: PubMed
Publication date: 2026/01/08
Xu WeikangShan JijunWang JifeiZhou YudiOuyang YimingChen YananlanZhou Qiyang - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that lacks effective targeted therapies. PKMYT1, a membrane-associated kinase involved in G2/M cell cycle regulation, is overexpressed in BC and associated with poor prognosis. However, the post-translational mechanisms regulating PKMYT1 stability remain largely unknown. In this study, we identified USP49 as a key deubiquitinase regulating PKMYT1 protein stability. Bioinformatic analysis of publicly available TNBC transcriptomic datasets revealed that USP49 is significantly overexpressed in TNBC tissues and correlates with unfavorable clinical outcomes. Consistently, USP49 expression was elevated in multiple TNBC cell lines. Functional assays demonstrated that USP49 knockdown reduced cell viability and colony formation, disrupted cell cycle progression, increased apoptosis, and suppressed migration and invasion. Mechanistically, USP49 was shown to interact with PKMYT1, limiting its ubiquitination and subsequent degradation. Overexpression of PKMYT1 restored the malignant phenotypes of USP49-deficient TNBC cells. Collectively, these findings uncover a novel USP49-PKMYT1 regulatory axis that drives TNBC progression. - Source: PubMed
Publication date: 2025/12/18
Chen JichengFu XinghangGao XiaotanSun YingmingXiao JianChen WenxinWang HebingYang BinglinZhang MaoquanChen YongtianWen YanmeiDeng HanqingChen ChangmingLuo Huatian - : 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