Ask about this productRelated genes to: UBE2M antibody
- Gene:
- UBE2M NIH gene
- Name:
- ubiquitin conjugating enzyme E2 M
- Previous symbol:
- -
- Synonyms:
- hUbc12, UBC12
- Chromosome:
- 19q13.43
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-22
- Date modifiied:
- 2016-03-14
Related products to: UBE2M antibody
Related articles to: UBE2M antibody
- Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and one of the best-characterized drivers is oncogenic Wnt signaling. In this study, we demonstrated that Orlistat, an FDA-approved anti-obesity drug, is a unique inhibitor of oncogenic Wnt signaling and CRC. We confirmed that the known target FASN was not associated with Orlistat inhibition of CRC, and identified the NEDD8-conjugating enzyme UBC12 (UBE2M) as a candidate target instead. The direct engagement of Orlistat and UBC12 was confirmed by ITC assay with a KD value of 678 nM. Of note, Orlistat inhibited the NEDD8-conjugating activity of UBC12 and blocked UBC12 interaction with DCN1 (defective in cullin neddylation 1), thereby selectively suppressing Cullin 1 neddylation. In addition, overexpression of UBC12 positively regulated Wnt/β-catenin signaling in normal cells, while depletion of UBC12 not only inhibited oncogenic Wnt signaling but also abrogated Orlistat's inhibition of Wnt signaling and cell proliferation in CRC cells. Taken together, our findings revealed UBC12 as a novel Orlistat target, and identified UBC12 as a potential therapeutic target for Wnt-dependent cancers. - Source: PubMed
Publication date: 2026/04/30
Shen MengzhenLi HuihuiXuan YingZhu HongyanChen LizheHao PiliangZhang ChengqianFang JiansongZhou XianglianYan RongQu YiKe Xisong - Ubiquitin-related modifier 1 (URM1) is an evolutionarily conserved ubiquitin-like protein. In eukaryotes, it serves dual roles as a sulfur donor for tRNA modification and a posttranslational protein modifier. URM1 is proposed to be a primitive protein modifier and a potential precursor to the more complex ubiquitin system. However, no specific activating enzyme (E1), conjugating enzyme (E2), or ligase (E3) has been reported for the URM1 modification cascade in human cells. In this study, we design an activity-based URM1 probe to covalently capture cysteine enzymes functioning in the URM1 signaling pathway. Through proteomic characterization and cell-based validation, we identify NAE1/UBA3 and UBE2M as E1 and E2 enzymes, respectively, for the urmylation pathway under both normal and oxidative stress conditions. Pharmacologic perturbation of the UBE2M-DCN1 module suggests DCN1 may contribute to URM1 conjugation. Bioinformatic analysis further reveals that genetic knockdown of NAE1, UBE2M, and URM1 affects overlapping genes associated with pathways controlling cellular response to stress conditions or with implications in liver diseases. URM1 serves a protective role against oxidative stress. Pevonedistat, a potent NAE1 inhibitor that blocks protein urmylation in human cells, exhibits strong synergy with cisplatin, an agent known to induce oxidative stress, in killing liver cancer cells effectively. - Source: PubMed
Publication date: 2026/04/29
Chakraborty SwatadiptaChanda SaibalCao ZhongwenPham AlanZhang ZihanWang YinshengHerring LoganCao WenyueLiu Wenshe Ray - Protein arginine methyltransferase 1 (PRMT1) is best known as a nuclear epigenetic writer that deposits the activating H4R3me2a mark. However, PRMT1 also methylates diverse non‑histone substrates across multiple cellular compartments, and this review moves beyond chromatin‑centric models to provide a substrate‑driven mechanistic framework in kidney and metabolic diseases. We analyze four validated substrate axes: FoxO1 in gluconeogenesis, BRD4 in fibrosis, UBE2m in fatty acid metabolism, and RelA in inflammation. These examples illustrate how PRMT1 integrates metabolic, inflammatory and fibrotic signals in a cell‑type‑specific manner. A key insight is functional pleiotropy: PRMT1 exerts opposing roles-restraining lipolysis in white adipose tissue while enabling thermogenesis in brown fat, and suppressing NF‑κB in renal tubules while promoting pro‑inflammatory macrophage polarization in the liver. This complexity challenges the view of PRMT1 as uniformly pro‑pathogenic. We critically evaluate the inhibitor landscape, including the terminated clinical trial of GSK3368715, and identify major translational barriers. We conclude that realizing therapeutic potential in chronic kidney and metabolic diseases requires a shift from broad inhibition toward context‑selective modulation-through substrate‑selective inhibitors, tissue‑specific delivery and biomarker‑guided strategies. - Source: PubMed
Publication date: 2026/04/26
Zhu YuHocher BertholdLiu Fanna - Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease involving immune dysregulation, metabolic reprogramming, and multi-organ damage. The Jieduquyuziyin prescription (JP), a contemporary Chinese herbal formula based on the Traditional Chinese Medicine principle of "Jiedu Quyu Ziyin," has shown clinical efficacy in SLE. This review aims to synthesize clinical and preclinical evidence explaining how JP achieves systemic therapeutic effects by targeting interconnected pathological pathways in SLE. - Source: PubMed
Publication date: 2026/04/14
Gan YihongLiu JingqunZhou ShihuiLin KeWang XinchangFan YongshengXu LiBao Jie - Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of childbearing age. Infertility caused by ovulatory disorders and low follicle quality is an urgent problem. Abnormal fatty acid oxidation (FAO) contributes critically to the etiology and progression in PCOS. However, the potential mechanism by which FAO affects follicular development in PCOS patients is unclear. Here, we demonstrate that increased expression of tripartite motif-containing protein 21 (TRIM21) (an E3 ubiquitin ligase) in the prenatal anti-Müllerian hormone PCOS mouse model leads to abnormal FAO in ovarian granulosa cells. Functionally, knocking down TRIM21 increased mitochondrial membrane potential homeostasis and improved fatty acid-dependent aerobic respiration and oxidative phosphorylation functions. TRIM21 regulated the ubiquitination and degradation of carnitine palmitoyltransferase 1A (CPT1A), a key enzyme for FAO, at the K161 site. TRIM21 is regulated by the E2 ubiquitin ligase ubiquitin conjugating enzyme E2 M (UBE2M), which enhances its protein expression and ubiquitination by TRIM21 neddylation. MLN4924 (a neddylation inhibitor) reversed the ubiquitination degradation of CPT1A by inhibiting TRIM21 neddylation. The phenotype of PCOS mice treated with MLN4924 was alleviated, and the maturation of oocytes and embryonic development improved. Together, these findings indicate that TRIM21-CPT1A plays an indispensable role in FAO of granulosa cells, and inhibiting TRIM21 neddylation may be a therapeutic strategy to improve abnormal follicular development in PCOS. - Source: PubMed
Publication date: 2026/04/03
Na XinniLiu JinchiTan YinanMeng LingboGuo CuishanZuo NaDai WanlinCong RuitingZhang BowenShi WantingHu JiaLiang JunzhiWei ShuangZhao ZhongyuChen JingQiao XinboLi Da