Ube2c inhibitor

 Ube2c inhibitor. Interestingly, this repression of UBE2C by wild-type p53 was observed at very early times of p53 induction suggesting that the effect was not secondary to normal cell cycle-regulated expression of UBE2C. Mar 10, 2022 · Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. Moreover, based on our findings, it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms. Oct 31, 2012 · Functional studies inhibiting UBE2C was found to enhance radiation and chemo-sensitivity in cervical cancer cell lines . Oct 31, 2012 · An increased expression of UBE2C (Ubiquitin-conjugating enzyme E2C) has been associated with high tumor grade and cancer progression. 30 µM) were mixed together in RBU (50 mM HEPES pH = 7. May 1, 2011 · UBE2C protein expression and UBE2C gene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situ hybridization in a TMA format. Drug repurposing, referred to rediscovering a new indication for an existing drug, has been appreciated for its less time-consuming and expensive, and reduced risk of unexpected side effects ( Pushpakom et al Dec 22, 2022 · Ubiquitin-conjugating enzyme E2C (UBE2C) mediates ubiquitylation chain formation via the K11 linkage. Then, we found that Nuclear Factor-κB (NF-κB) inhibitor, pyrriolidine-dithiocarbamate (PDTC), could inhibit NF-κB p65 nuclear translocation and UBE2C expression, which was partially reversed by ECRG4 Although no specific UBE2C inhibitors are currently available for clinical use, proteasome inhibitors form a novel class of chemotherapeutic agents that lead to cell cycle arrest and cell death. generate a potent and specific small-molecule inhibitor of the E1 ubiquitin-activating enzyme UBE1 that has antitumor activity in mice against a wide variety of tumor types. EA-derived cells expressing UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C, suggesting that patients with EAs overexpressing UBE2C may benefit from agents targeting this ubiquitin-conjugating enzyme. Jul 7, 2011 · Here we demonstrate that the G1/S cell-cycle inhibitor-779 (CCI-779), an mTOR inhibitor, inhibited UBE2C mRNA and protein expression in AR-positive CRPC cell models abl and C4-2B. A high UBE2C protein expression level has been reported in various types of human tumors. (B) Extract was pre-incubated with DMSO or compounds. Sep 4, 2020 · UBE2C is highly expressed in breast microcalcification lesions and its overexpression is correlated with relapse in early HR + /HER2 − breast cancer patients . Non-small cell lung cancer (NSCLC; approximately 85% of patients) and small cell lung cancer (SCLC; approximately 15% of patients) are the two main forms of lung cancer, and NSCLC is classified into three types, namely adenocarcinoma, squamous cell Nov 12, 2019 · UBE2C, a ubiquitin-conjugating enzyme, accepts ubiquitin from E1, transfers it to specific anaphase-promoting complex/cyclosome (APC/C) substrates and catalyses lys-11- and lys-48-specific polyubiquitination, finally contributing to degradation of the APC/C substrates via the ubiquitin–proteasome system and promoting mitotic exit and cell Mar 17, 2023 · Cells were cotreated with the autophagy pharmacologic inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C In addition, Pearson's correlation analysis demonstrated a negative correlation between the mRNA levels of ECRG4 and UBE2C in ESCC tissues. May 9, 2017 · P5091 accelerated the degradation of AR and V7 isoform affecting PSA, UBE2C, CDC20 transcription and PC cells proliferation. Apr 18, 2024 · Besides, the application of proteasome inhibitor reduced cellular ROS and Fe 2+ levels after UBE2C knockdown (P < 0. Feb 6, 2017 · UBE2C expression fluctuates during the cell cycle, peaking at prometaphase to regulate chromosomal segregation and decreasing in anaphase. Jun 1, 2023 · Cells were cotreated with the autophagy pharmacologic inhibitors chloroquine and/or bafilomycin A1, and mRFP-GFP-LC3 assays were performed to monitor autophagic flux and determine whether UBE2C suppresses the autophagy program. Currently, the scarcity of UBE2C inhibitors is alarming. UBE2C After that HA- UbVS was added. In this study, we aimed to analyze its role and mechanism in cancer by combination of bioinformatic analysis and experimental validation. 011, HR = 1. Jun 1, 2022 · Multiple studies have shown that UBCH10 (UBE2C gene) mRNA is overexpressed in many cancer cell lines and primary tumors as compared to normal tissues [17], [18], [19]. UBE2C protein expression and UBE2C gene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situ hybridization in a TMA format. HGNC Approved Gene Symbol: UBE2C. Feb 10, 2023 · Peptides were found to be more suited to the large or flat PPI surfaces, in addition to their better pharmacokinetic properties. Disorders associated with UBE2C include methotrexate-related lymphatic hyperplasia and complement component 7 deficiency. In this study, we found that UBE2C was elevated in this human pan-cancer analysis, and high expression of UBE2C was correlated with poor prognosis. XL-188 is the USP7 inhibitor (USP7i) and XL-233 is the related inactive control compound. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0. Aug 1, 2022 · It is still urgently needed to design or search for a specific Ube2c inhibitor for testing its autophagy-promoting and anti-AD effects. In addition Apr 1, 2023 · UBE2C (Ubiquitin conjugating enzyme E2 C), a key regulator of cell cycle progression, is a promising target for discovery of antitumor agents. It is an essential indicator of the mitotic destruction events. 5 µM), UBE2D1 (13. In addition, patients with low expression of UBE2C had higher sensitivity to adriamycin and low expression of UBE2C was also sensitive to 5-fluorouracil and sorafenib . 93). PC9 cells showed a higher UBE2S expression and migrative ability than H460 cells. 3D). Moreover, we showed that combination treatment of DTX and an inhibitor of mitotic exit can exert synergistic effect in high ARV7-expressing prostate cancer cells. The ubiquitin-conjugating enzyme 2C (UBE2C) is the key component in the ubiquitin proteasome system (UPS) by partnering with the anaphase‑promoting complex (APC/C). UBE2C is associated with proliferation, migration and invasion of HCC. . There hasn’t been reported that p21 is regulated by UBE2C in human granulosa cells. The results of survival analysis showed a close relationship between UBE2C and BC. Compared with placebo, olaparib improved median pro-gression-free survival from 3. Apr 17, 2019 · Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. 10, 11 Additionally, during cell mitosis, UBE2C can mediate the degradation of securin, an inhibitor of the separase enzyme, thereby with 5,6-diamino-2,4-pyrimidinediol (1:1) and 7-alpha-d-ribofuranosyl-2-aminopurine-5’-phosphate may act as best inhibitors and further in vitro studies, may lead to development of novel and best inhibitor of UBE2C. Tumor cells are more susceptible to proteasome inhibition due to their rapid division and disordered regulatory pathways. In so doing, we generated an inhibitor of substrate priming by UBE2C that stabilizes APC/C targets in mitotic extracts. This study aimed to determine the prognostic value of UBE2C in invasive breast cancer (BC). A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. 12 Genomic coordinates (GRCh38): 20:45,812,644-45,816,952 (from NCBI) The regulated destruction of mitotic cyclins A (see 604036) and B (see 123836) near the end of mitosis is essential for the inactivation UBE2C protein expression and UBE2C gene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situ hybridization in a TMA format. Key words: Glide, UBE2C, ADME/T and Docking. Aug 2, 2018 · Additionally, the ERK1/2 inhibitor U0126 was used to confirm the signaling pathway involved in UBE2C-mediated cancer progression. 02). On the other hand, overexpression of this enzyme led to enhanced ERK signaling and proliferation of cancer cells. 8g). UBE2C protein and mRNA expression were Jan 15, 2018 · Hyer et al. 6G). In addition to its well-known role in cyclin B destruct … Mar 15, 2023 · UBE2C is an E2 enzyme and a transient binding partner of the anaphase promoting complex (APC/C), which is required to facilitate APC/C-mediated ubiquitylation of cyclin B1 and securin 16,17. doi: 10. Sep 27, 2013 · Finally, it has been shown that inhibition of ubiquitin conjugating enzyme UBE2C reduces proliferation and sensitizes breast cancer cells to letrozole-an aromatase inhibitor-tamoxifen etc. 10-1. However, little is known about the precise mechanism by which UBE2C expression is downregulated in gastric cancer. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be overexpressed in human cancers and act as a potential oncogene. May 11, 2020 · In silico mining of total RNA-seq analysis revealed that the Ube2h, Ube2l6, Ube2b, Ube2c, Ube2o and Ube2m genes were highly expressed in the primary cortical neurons (Figure 1 A–F). In NMR experiments, adding the UbV inhibitor to labeled UBE2C and either APC11 RING domain or APC2 winged-helix B (WHB) domain, only binding with the APC2 domain resulted in CSPs, indicating that a dimeric UbV Results We uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. KAT2A, E2F1, and UBE2C were formed with the Transcripts Per Million (TPM) mean of each mRNA expression of samples in TCGA, and the exact sample sizes of cancer and normal samples used are reported in Table S1. 2. 8 to 7. 050). Taken together, these results suggest that at least six Ube2 subfamily gene expressions were well conserved in the cortical neurons. UBE2M is an E2 There was a positive correlation between high UBE2C protein expression and cell cycle-associated biomarkers, p53, Ki67, EGFR and PI3K. Kaplan–Meier plotter was used to assess the Nov 14, 2018 · For E2 charging, recombinant GST-UBA1 (280 nM), UBE2R1 (8. Interestingly, blockade of ERK signaling by its inhibitor, U0126, reversed UBE2C-induced oncogenic phenotypes. Feb 25, 2021 · Cox regression analysis has indicated UBE2C could function as the independent prognostic factor of prostate cancer. Strikingly, UBE2C was the gene with the highest differential expression between tumor and normal tissues among 12,535 transcripts [20]. Immunological analyses identified UBE2C + CD8 + T cells as adverse prognostic factors, suggesting their potential as biomarkers for patient stratificat … Feb 13, 2023 · UBE2C is regulated by DNA primase subunit 1 to mediate the ubiquitination of p53 (55,56). May 27, 2022 · In summary, this study shed light on the potential roles of UBE2C, UBE2T, UBE2S on diagnostic and prognostic biomarkers for HCC. 35 Furthermore, the mTOR inhibitor CCI-779 decreased the levels of UBE2C in castration-resistant prostate cancer, by disrupting its Nov 1, 2019 · Furthermore, silencing of UBE2C in these cells correlated with the interruption of cell cycling at the G2/M stage. A dominant negative form of UBE2C (DN-UBE2C The protein level of UBE2S was higher in PC9 cells than in H460 cells, which was opposite to that observed for IκBα. Jul 14, 2011 · In this study, we showed that the G 1 –S cell-cycle inhibitor-779 (CCI-779), an mTOR inhibitor, inhibited UBE2C mRNA and protein expression in AR-positive CRPC cell models abl and C4-2B. Mar 26, 2021 · In addition, UBE2C, UBE2D2, UBE2D3 , UBE2N, UBE2Q1, UBE2S, and UBE2T can affect the stability and activity of p53 protein to mediate cell cycle arrest. 3a). The Neoadjuvant ICBs plus chemotherapy shows promising efficacy in locally advanced EC, with MPR being a significant predictor of lower recurrence risk. Next, we treated HCT116p53 +/+ cells with the DNA-damaging agent 5-FU and observed significant reduction in UBE2C mRNA expression in a time-dependent manner when compared with an untreated set (Fig. A further implication of this finding is that Jun 22, 2021 · Western blot analysis revealed significant down-regulation of AR, ARv7, UBE2C, SAM68, FOXA1 and upregulation of cleaved PARP and cleaved CASPASE 3. Moreover, P5091 accelerated the degradation of CCDC6 sensitizing the cells to PARP-inhibitors, that acted sinergistically with genotoxic agents. UBE2C expression is elevated and predicts poor prognosis in hepatocellular carcinoma, esophageal squamous cell carcinoma and intestinal-type gastric cancer [14,26,27]. Microcalcification (MC) is the most common mammographic feature of early breast cancer. The immunohistochemical analys … Feb 22, 2023 · M435-1279, an inhibitor of UBE2T, blocks the UBE2T-mediated RACK1 degradation to inhibit the overactivation of Wnt/β-catenin, thereby inhibiting the proliferation and progression of GC . The ubiquitination of PER1 was then detected in UBE2C WT and UBE2CC114S plasmid-overexpressing cells. Thus, there is a need to further explore the role of UBE2C in malignant brain cancer and to develop effective targeted therapies for patients with this deadly disease. Quantification of protein concentration was performed according to the BCA protein quantification kit. Jun 26, 2023 · Everolimus, an mTOR inhibitor, has antitumor and antiangiogenic activity and has been shown to improve progression-free survival in patients with vascular endothelial growth factor receptor-tyrosine kinase inhibitors 45. While previous in vitro studies showed that UBE2C plays a growth-promoting role in cancer cell lines, the underlying mechanism remains elusive. The supernatant was collected by centrifugation at 12,000 g for 15 min at 4ºC. Oct 20, 2021 · The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. IU1–47 is the USP14 inhibitor (USP14i) and IU1-C is the related inactive control compound. As a conjugating enzyme, it directs polyubiquitination to preferred lysine in the substrates. Conclusions: UBE2C was pivotal for the progression of prostate cancer and the treatment with the HIF-1α inhibitor (PX478) significantly reduced porcine AV calcification in static and d-flow conditions. Jun 12, 2020 · Background A comprehensive investigation of ubiquitin-conjugating enzyme E2I (UBE2I) in cancer is still insufficiency. GSEA showed UBE2C had played an important role in the pathway of prostate cancer, such as NOTCH signaling pathway, WNT-β-catenin signaling pathway. Oct 6, 2023 · Using 10. Background: The ubiquitin conjugating enzyme 2C (UBE2C) protein is an Correction to: CDK4/6 inhibitors downregulate the ubiquitin-conjugating enzymes UBE2C/S/T involved in the ubiquitin-proteasome pathway in ER + breast cancer Clin Transl Oncol . Treatment with CCI-779 significantly decreased abl cell proliferation in vitro and in vivo through inhibition of cell-cycle progression of both G 2 –M and Jul 24, 2023 · The protein synthesis inhibitor cycloheximide (CHX) and proteasome inhibitor MG132 were then applied, and PER1 degradation was found to be significantly inhibited by MG132 (Fig. High UBE2C protein expression was an independent predictor of poor outcome (p = 0. Remarkably, this strategy also identified the UBE2C-binding site on the APC2 cullin domain as a previously unknown Ub-binding exosite with preference for K48-linked chains. Apr 3, 2024 · GeneCards Summary for UBE2C Gene. Tumor cells are more susceptible to proteasome inhibition due to their rapid division and disordered regulatory pathways, and bortezomib has now been Jun 6, 2018 · The transition between early mitotic inhibitor 1 acting as a substrate of the APC/C and as an inhibitor of the same complex results in an irreversible switch that mediates human cell-cycle commitment. Transcriptional Expression of Different Genes in Pan-Cancer. ERK1/2 inhibitor U0126 (10 μmol/L) decreased the phosphorylation of the ERK1/2 caused by UBE2C overexpressing SGC7901 cells. Lung cancer is one of the leading cancer types for the estimated new cancer cases and deaths according to the cancer statistics []. Thus, these results imply that UBE2C knockdown sensitizes ferroptosis of AML cells in a proteasome-dependent manner. Oct 17, 2023 · P21 is a CDK inhibitor and is known as cyclin-dependent kinase inhibitor 1A (CDKN1A). The Oct 8, 2022 · 2. Treatment with CCI-779 significantly decreased abl cell proliferation in vitro and in vivo through inhibition of cell-cycle progression of both G2/M and G1/S phases Feb 6, 2022 · The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. Oct 27, 2023 · All these findings suggest that UBE2C is closely associated with the development of cancer and could be a potential therapeutic target for different types of cancers. Apr 3, 2014 · Ubiquitin-conjugating enzyme 2C (UBE2C) contributes to ubiquitin-mediated proteasome degradation of cell cycle progression in breast cancer. A proteome-wide screen previously conducted in the Shah lab has identified UBE2C as a direct substrate of LIMK2 using an Jul 1, 2016 · UBE2C was found to be repressed at the mRNA and protein levels both upon ectopic expression of wild-type p53 or its induction by DNA damage. After 20 minutes, samples were processed for immunoblotting. The encoded protein is necessary for the destruction of mitotic cell cyclins and cell cycle progression, and may be involved in cancer progression. Especially, it is unknown whether down-regulation of Ube2c can promote autophagy and Aβ clearance, thereby improving the learning and memory of AD. This study is the first to report UBE2C post-translational modulation mediated by LIMK2 kinase. Jul 1, 2016 · We observed a dose-dependent decline in the expression of UBE2C upon ectopic expression of wild-type p53 protein in HCT116p53 −/− cells (Fig. In addition to its well-known role in cyclin B destruction that is essential for exit from mitosis, UBE2C also plays an important role in mitotic Aug 2, 2022 · Therefore, our finding suggests a link between CDK4/6 inhibitors to the UBE2C/UBE2S – APC/C mediated ubiquitination and protein degradation. 1 A). The effect of the proteasome inhibitor bortezomib and small-interfering RNA knockdown was assessed by apoptotic assays and immunoblotting. 1007/s12094-022-02928-2. However, it is challenging to develop inhibitors of UBE2C owing to its lack of “druggable” pockets. CCI779 is an mTOR inhibitor; its anti-cancer activity has been demonstrated in colorectal carcinoma and prostate cancer [ 28 , 29 ]. Conclusions- These results suggest that miR-483 and UBE2C and pVHL are novel flow-sensitive anti- and pro-calcific AV disease molecules, respectively, that regulate the HIF-1α pathway in AV. In consistent, silencing UBE2C abrogated the enhancement of growth and sorafenib resistance induced by PRIM1 overexpression in HepG2-derived spheroids (Additional file 6: Figure S6A and B). UBE2C (Ubiquitin Conjugating Enzyme E2 C) is a Protein Coding gene. UBE2C may, therefore, serve as a potential therapeutic target aimed at inducing radiation and chemo sensitization. In this study, computational methods was used in order to verify whether peptide drug inhibitors are good drug candidates against the ubiquitin protein, UBE2C by conducting docking, MD and MMPBSA analyses. Conclusion: This study indicates that UBE2C is an independent prognostic biomarker in BC Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM-1 microM) showed decreased proliferation (P = . Consistent with our hypothesis, the silencing of UBE2C or CDK1 inhibited Wnt-3a expression in A549/NCI0H1299 cells, and limited influenced was found Moreover, treatment with the HIF-1α inhibitor (PX478) significantly reduced porcine AV calcification in static and d-flow conditions. 35 Furthermore, the mTOR inhibitor CCI-779 decreased the levels of UBE2C in castration-resistant prostate cancer, by disrupting its Oct 31, 2023 · UBE2C has also been proven as a promising therapeutic target, despite the lack of specific inhibitors. 4D). Oct 17, 2022 · Although the NAE inhibitor MLN4924/pevonedistat is currently under clinical investigation as an anti-cancer agent, there are no small molecules available that selectively target UBE2F. us, pancreatic cancer remains a deadly malig- UBE2C is a shear-dependent target of miR-483 and regulates DF- and miR-483-induced inflammation and EndMT in HAVECs. For samples that May 5, 2022 · UBE2C protein, encoded by gene UBE2C, was reported to exacerbate cell apoptosis and contribute to chromosome mis-segregation during the formation of tumors. Apr 28, 2023 · UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Our results show that inhibition of UBE2C sensitizes breast cancer cells to radiation, doxorubicin and hormone blocking agents. 45, 95% CI; 1. Methods The expression profile of UBE2I in human cancers were obtained using GEPIA. In parallel with the recent study that reported proteosomal activation , our study potentially expands the ever-increasing roles of CDK4/6 inhibitors into the field of protein degradation. Sep 27, 2013 · Purpose The objective of this study was to determine radiation, doxorubicin, tamoxifen and letrozole sensitivity of breast cancer cells in response to functional inhibition of the ubiquitin conjugating enzyme UBE2C. Here, we report, for the first time, the discovery, via structure-based virtual screen and chemical optimization, of such a small molecule, designated as HA-9104. Diseases associated with UBE2C include Complement Component 7 Deficiency and Gastric Cancer . 01, Fig. 6D), similar to the effect of Ube2c knockdown (Fig. Dec 19, 2023 · The corresponding experimental cells were lysed with 1% protease inhibitor. Jun 1, 2023 · AbstractRecent studies have shown that autophagy plays an important role in gynecologic tumors, and ubiquitin modification of autophagy regulatory components is essential to regulate autophagic flux. [139 Apr 18, 2023 · UBE2C is a component of a protein complex called APC/C, and it controls progression through the final stage of the cell cycle (termed mitosis). Ubiquitin-conjugating enzyme 2C (UBE2C) participates in cell cycle progression and checkpoint control by targeted degradation of short-lived proteins. p53 acts as a homotetramer transcription factor, regulating the expression of genes including transactivation of its target genes, including cyclin dependent kinase inhibitor 1A (CDKN1A, also Oct 31, 2023 · UBE2C has also been proven as a promising therapeutic target, despite the lack of specific inhibitors. Nov 16, 2023 · UBE2C belongs to the E2 ubiquitin-conjugating enzyme family and mainly delivers ubiquitin to target proteins such as CyclinA and Cyclin B through APC/C, thereby ensuring orderly progression of the cell cycle. Similarly, in HCC, UBE2T inhibition mediated by small interfering (si)RNA inhibits the proliferation and colony formation of GC cells by promoting G 2 /M Feb 23, 2021 · Further exogenous UBE2C enhanced the resistance of the spheroids against sorafenib (Fig. KPT-8602 with or without olaparib was shown to reduce homologous recombination-regulated DNA damage response targets including BRCA1 , BRCA2 , CHEK1 , EXO1 , BLM , RAD51 , LIG1 , XRCC3 and RMI2 . 4B–C), and also suppressed Erastin-induced cell death upon UBE2C knockdown (P < 0. Jan 9, 2021 · Furthermore, we also identified E2 enzyme UBE2C as the primary downstream effector of ARV7 in promoting the SAC inactivation and premature degradation of cyclin B1. Cytogenetic location: 20q13. We found in MGC‑803 Aug 1, 2022 · However, the exact roles of Ube2c over-expression in AD are still unclear, and the association of Ube2c with autophage, amyloid pathology and cognitive deficits in AD remains to be clarified. a,b) UBE2C expression was increased in HAVECs exposed to d-flow (DF) compared to s-flow (SF) for 24 hours, as determined by Western blot and its quantification by ImageJ (n=3). 2022 Nov;24(11):2251-2253. The connection between PI3K/Akt/mTOR pathway and UBE2C has been previously reported in gastric cancer cells, where UBE2C led to the activation of AURKA and consequent EMT by the decrease in p-AKT1 levels. Cyclin-dependent kinases (CDKs) are important regulators in the progression of the cell cycle [ 46 ]. However, little is known about the functional roles of UBE2C in … Dec 30, 2020 · As shown in Figure 6A for nine different types of cancer cell lines, the gene (UBE2C) regulated by the mTOR inhibitor had the same gene-drug correlation trend. Apr 27, 2022 · Ubiquitin-Conjugating Enzyme E2 C (UBE2C) is a gene that encodes protein. 5 Feb 17, 2017 · Although no specific UBE2C inhibitors are currently available for clinical use, proteasome inhibitors form a novel class of chemotherapeutic agents that lead to cell cycle arrest and cell death. Still unknown is whether and how UBE2C plays a promoting role in vivo. Aug 31, 2020 · Through this, a UBE2C inhibitor and a Ub-binding exosite on APC2 domain that preferentially binds K48-linked chains were discovered []. Electron microscopy observation of Results: We uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Further validation in the HR(+) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. Methods UBE2C was evaluated using the Molecular Taxonomy of Breast Cancer International Consortium (n = 1980), The Cancer Genome Atlas (n Apr 28, 2021 · 1. One plausible Apr 28, 2023 · The connection between PI3K/Akt/mTOR pathway and UBE2C has been previously reported in gastric cancer cells, where UBE2C led to the activation of AURKA and consequent EMT by the decrease in p-AKT1 levels. 1 B). UBE2C has been shown to be preferentially over expressed in cancers compared to 17 other E2 genes . Conclusions—These results suggest that miR-483 and UBE2C and pVHL are novel flow-sensitive anti- and pro-calcific AV disease molecules, respectively, that regulate the HIF-1α pathway in AV. Apr 25, 2024 · UBE2C is upregulated in castration-resistant prostate cancer and shows strong correlation with high tumor grade. 4 months, but there is no signicant dierence in overall survival between the groups. Overexpression of gene UBE2C has been found in tumor cells of HCC patients compared to noncancerous liver cells in 62 out of the studied 65 clinical cases[ 11 ]. Overexpression of UBE2C causes the missegregation of chromosomes (aneuploidy), chromosome misalignment and lagging, mitotic slippage and increased number of centrioles, in addition to a decrease in cyclin B1 Jan 19, 2005 · UBIQUITIN-CONJUGATING ENZYME E2C UBIQUITIN-CONJUGATING ENZYME UBCH10; UBCH10. Feb 6, 2022 · Background The Ubiquitin-conjugating enzyme 2C (UBE2C) is essential for the ubiquitin–proteasome system and is involved in cancer cell migration and apoptosis. Methods Taqman Real time PCR was performed to measure UBE2C levels in breast cancer cell lines and control HBL100 and HEK293T cells. 73 µM) or UBE2C K119R or UBE2C C114S (11. Aug 8, 2019 · In so doing, we generated an inhibitor of substrate priming by UBE2C that stabilizes APC/C targets in mitotic extracts. Phosphorylation of IκBα was not changed by treatment with the IKK-specific inhibitors PS1145 and SC514 in PC9 and H460 cells. Introduction. In this manuscript we describe computational studies to design specific inhibitors for UBE2C. These evidences suggested that PRIM1 might contributed to May 15, 2023 · To assess whether the UBE2C/CDK1 axis played a role in the regulation of Wnt/β-catenin signaling, we treated A549/NCI-H1299 cells with UBE2C and CDK1 siRNA for 48 hours (Figure 3C and and3D). In this study, we evaluated whether UBE2C could be a tumor marker of early breast cancer with MC found on screening mammography. 72 as UBE2C expression cutoff, patients with higher UBE2C mRNA level (n = 287) showed poorer overall prognosis compared with those with lower UBE2C mRNA level (n = 280) (Fig. Among its related pathways are Regulation of activated PAK-2p34 by proteasome mediated degradation and APC-Cdc20 mediated degradation of Nek2A . In this study, we found that the ubiquitin-conjugating enzyme E2C (UBE2C) affects endometrial cancer cell apoptosis and proliferation by inhibiting autophagy. This study expands the upstream regulatory mechanism of mTOR signaling, which is regulated by FOXM1-ZIC2-UBE2C axis. 5 µM) and bioUBB (8. Nov 10, 2021 · Growing evidence has demonstrated that UBE2C plays a critical role in cancer progression, but there is no study focusing on the prognosis, upstream regulation mechanism, and immunological roles of UBE2C across diverse tumor types. However, inhibitors specifically targeting UBE2C remain undiscovered, but there is evidence that a potential target for the proteasome inhibitor bortezomib may be UBE2C . inhibitors, such as olaparib, have gained approval for use in patients with germline BRCA1 or BRCA2 mutation [5]. Dec 16, 2011 · Ubiquitin-conjugating enzyme 2C (UBE2C) participates in cell cycle progression and checkpoint control by targeted degradation of short-lived proteins. dx xv qd bx en pv na da dk yz