Ask about this productRelated genes to: USP37 antibody
- Gene:
- USP37 NIH gene
- Name:
- ubiquitin specific peptidase 37
- Previous symbol:
- -
- Synonyms:
- KIAA1594
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-04
- Date modifiied:
- 2015-08-26
Related products to: USP37 antibody
Related articles to: USP37 antibody
- Cellular senescence, a state of permanent cell cycle arrest, contributes to tissue dysfunction and aging through the accumulation of apoptosis-resistant senescent cells. Although the transcription factor FOXO4 is known to enhance senescent cell survival, the mechanisms regulating its stability have remained unclear. Here, we identify a DNA damage response (DDR)-driven CHK2-USP37-FOXO4 axis essential for maintaining the apoptotic resistance of senescent cells. We demonstrate that FOXO4 protein stability is elevated in stress-induced senescent cells, resulting from reduced ubiquitin-proteasomal degradation. A deubiquitinase screen identified USP37 as the key enzyme stabilizing FOXO4 through direct interaction and removal of K48-linked polyubiquitin chains. Depletion of USP37 destabilizes FOXO4 and sensitizes senescent cells to apoptosis. Mechanistically, persistent DDR signaling during senescence activates CHK2, which phosphorylates USP37 at Thr589, thereby enhancing its binding to FOXO4. Importantly, ablation of USP37 in senescent cells increases the rate of apoptosis, a phenotype that is rescued by FOXO4 reexpression. Together, our work unveils USP37 as a CHK2-regulated stabilizer of FOXO4 that maintains the apoptotic resistance of senescent cells, suggesting the CHK2-USP37-FOXO4 axis as a therapeutic target for age-related pathologies. - Source: PubMed
Publication date: 2026/04/14
Sun JiahuiGeng AnkeSong ZhiweiChen LingjiangZhang Zhen-NingJiang YingMao Zhiyong - In aged humans and mice, hypobranched glycogen aggregates, known as polyglucosan bodies (PGBs), accumulate in hippocampal astrocytes. While PGBs are linked to cognitive decline in neurological diseases, they remain largely unstudied in the context of typical aging. We show that PGBs arise in autophagy-dysregulated astrocytes in the aged hippocampus, with substantial variation among 32 inbred BXD mouse strains. Genetic mapping through quantitative trait locus analysis identified a major locus (Pgb1) that modulates hippocampal PGB burden. Extensive transcriptomic and proteomic datasets were produced for the aged hippocampus of the BXD family to investigate the mechanism by which the Pgb1 locus modulates PGB burden. We identified that Pgb1 contains allelic Smarcal1 and Usp37 variants and influences PGB burden through trans-regulation of mRNA and protein expression levels, including abundance of glycogen-mobilizing factor PYGB. Furthermore, comprehensive phenome-wide association scans, transcriptomic analyses, and direct behavioral testing demonstrated that cognition remains intact despite age-related PGB burden. A record of this paper's transparent peer review process is included in the supplemental information. - Source: PubMed
Publication date: 2026/02/02
Gómez-Pascual AliciaGlikman Dow MNg Hui XinTomkins James ELu LuXu YingAshbrook David GKaczorowski CatherineKempermann GerdKillmar JohnMozhui KhyobeniOhlenschläger OliverAebersold RudolfIngram Donald KWilliams Evan GJucker MathiasOverall Rupert WWilliams Robert Wde Bakker Dennis E M - Background Breast carcinoma is one of the leading causes of cancer-associated mortality in women worldwide. Although several advances have been made in molecularly classifying breast cancers, treatment resistance continues to limit the overall survival. The Cancer Genome Atlas (TCGA) has unraveled diverse genomic alterations in breast carcinoma. However, some potential biomarkers still remain unexplored, like SETDB1, a histone methyltransferase involved in epigenetic silencing of tumor suppressor genes. ARMCX5 and SLCO6A1 are also some of the unexplored genes that could have a potential role in drug resistance. Materials and methods The Mutation Annotation Format (MAF) data set from the Cancer Genome Atlas Breast Cancer (TCGA-BRCA) cohort was analyzed using the Maftools, Survival, Mclust, and Survminer R packages. Oncodrive driver analysis and protein family (PFAM) domain mapping were performed. A total of 845 cases of breast carcinoma with complete survival data were retrieved, of which mutation data for 800 cases were available. Comprehensive mutation analysis was also done to unveil unexplored genes. Survival data of 845 cases were integrated for Kaplan-Meier and Cox proportional hazard analysis to ascertain the prognostic significance of an array of genes. Oncogenic signaling pathway mapping was done to determine the clinical enrichment of the genes associated with breast carcinoma. Genes associated with clinical enrichment, clustering of somatic mutations, and prognosis were subjected to further analysis. Results Besides the established molecular drivers like PIK3CA and TP53, we found several novel and understudied genes with potential prognostic and oncogenic significance. SETDB1 (p < 0.0001), USP37 (p < 0.0001), NDUFS1 (p = 0.025), TRPM4 (p < 0.0001), and MYO18A (p < 0.0001) were associated with poor prognosis. ARMCX5 (p < 0.0001) and SLCO6A1 (p < 0.0001) were enriched in high-grade tumors. Conclusion The TCGA-BRCA cohort analysis emphasizes a potential interplay of metabolic genes like NDUFS1, TRPM4, ARMCX5, SLCO6A1, and epigenetic axis genes like SETDB1 and USP37 in the oncogenesis and prognosis of breast carcinomas. These observations could open potential avenues for exploring novel therapeutics in aggressive breast carcinomas. - Source: PubMed
Publication date: 2025/12/07
Butta RamanButta Shristi - The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor (CDKI)-p27. This finding suggested a tumor suppressive function for USP37. Interestingly, the current study also uncovered Raptor, a component of the mTORC1 complex, as a novel target of USP37. Under conditions of low-USP37 expression, reduced Raptor stability and mTORC1 activity caused a decline in phosphorylation of 4E-binding protein 1 (4EBP1) and increased its interaction with eukaryotic elongation factor 4E (eIF4E), which is known to inhibit CAP-dependent translation initiation. Surprisingly, a subset of patients with SHH-driven medulloblastomas with elevated expression of USP37 and the Glioma-associated Oncogene 1 (GLI1), also exhibited poor outcomes. Using genetic and biochemical analyses, we showed that USP37-mediated stabilization of GLI1, a terminal effector of SHH signaling, increases pathway activity and upregulates expression of its target oncogene product, CCND1, to drive cell proliferation. These data indicate that USP37 elevation in SHH-driven medulloblastomas has the potential to promote non-canonical activation of SHH signaling. Overall, our findings suggest that USP37 may have context-specific oncogenic and tumor suppressive roles in medulloblastoma cells. - Source: PubMed
Publication date: 2025/12/18
Singh AshutoshCheng DonghangHaltom Amanda RYang YanwenDobson TaraHatcher RashiedaRajaram VeenaGopalakrishnan Vidya - : 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