Ask about this productRelated genes to: MDM2 antibody
- Gene:
- MDM2 NIH gene
- Name:
- MDM2 proto-oncogene
- Previous symbol:
- -
- Synonyms:
- HDM2, MGC5370
- Chromosome:
- 12q15
- Locus Type:
- gene with protein product
- Date approved:
- 1993-12-10
- Date modifiied:
- 2017-12-01
Related products to: MDM2 antibody
Related articles to: MDM2 antibody
- Colorectal cancer (CRC) remains the most prevalent malignancy of the digestive system globally and ranks second in cancer-related deaths worldwide. Metabolic reprogramming is one of the hallmarks of cancer. Aspartate is a proteinogenic non-essential amino acid with several essential functions in cancer cells. SLC1A3 is the main aspartate transporter, but its role in CRC needs to be elucidated. We found that SLC1A3 is significantly overexpressed in CRC tissues compared to adjacent normal tissues, and elevated SLC1A3 expression is associated with poor prognosis. Further, SLC1A3 could enhance the proliferation, invasion, migration of CRC cells and organoids by activating the DAG/PKC/MDM2 signaling axis. In addition, we revealed that SLC1A3 in CRC cells could induce the immunosuppressive M2 phenotype of macrophages via upregulating IL17c and CSF2. In sum, these findings suggest that SLC1A3 plays a dual role in CRC progression and may represent a promising target for therapeutic intervention. - Source: PubMed
Publication date: 2026/04/26
Deng ChaoZhou YouSong SijieLiu HongtaoLiao SiqiZhou LiChen SiyuanZhou ZhihangHe SongLiu Bingrong - Protein-protein interactions (PPIs) govern essential cellular processes, such as signal transduction, enzymatic catalysis, and the formation of macromolecular complexes, but their broad and dynamic interfaces often lack deep binding pockets, making it difficult for them to target conventional small molecules. Macrocyclic peptides have emerged as a powerful alternative, bridging the gap between small molecules and biologics and providing the structural flexibility for targeting extended protein surfaces with high specificity and affinity. The limitations of early efforts to modulate PPIs with linear peptides began to shift with the discovery of naturally occurring cyclic peptides and the development of phage display technologies, which demonstrated that conformational constraint could enhance the affinity and proteolytic resistance of peptides. Recent literature studies reveal a clear trend toward targeting disease-driving PPIs, particularly in oncology, such as MDM2-p53, BCL-2 family interactions, and KRAS-effector complexes, along with growing applications in infectious and inflammatory diseases. High-throughput screening technologies, structure-based drug design, and artificial intelligence techniques have facilitated the identification and prediction of novel peptide-based drugs. Various chemical modification techniques, including hydrocarbon stapling methods, cyclization from head to tail, and the addition of unnatural amino acids, have increased peptide stability and developed their capacity to cross cellular membranes. This review investigates the recently established and emerging strategies for discovering macrocyclic peptide-based PPI modulators, highlighting their application in targeting diverse diseases, thereby expanding the scope of precision medicine, and concludes with a discussion on the future directions in the field of PPI-directed peptide-based drug development. - Source: PubMed
Publication date: 2026/04/22
Sunny Erin AnnSadanandan Sandhya - Antibody-drug conjugates (ADCs) and bispecific antibodies (BiAbs) are emerging treatments for small cell lung cancer (SCLC). However, optimal patient selection remains unclear. Delta-like ligand 3 (DLL3) is a promising therapeutic target, but its clinical utility is not fully established, and data on other targetable proteins such as trophoblast cell-surface antigen 2 (TROP2) and B7-H3 remain limited. To our knowledge, no prior study has assessed multiple therapeutic targets within the same patient before and after treatment. This study examined changes in DLL3 and other targets in de novo and transformed SCLC. - Source: PubMed
Publication date: 2026/04/17
Murata SaoriKashima JumpeiHorinouchi HidehitoKishikawa SatsukiMasuda KenShinno YukiOkuma YusukeYoshida TatsuyaGoto YasushiYamamoto NoboruWatanabe Shun-IchiMatsumoto YujiOkuma KaeYatabe Yasushi - Chronic stress significantly impacts hippocampal function through transcriptional and epigenetic mechanisms. While the roles of lncRNAs in stress-related transcriptional and epigenetic regulation have recently been recognized, their genome-wide functions controlling the transcriptional network remain largely unclear. Evidence indicates that the lncRNA uc.104 is involved in stress responses; however, its genome-wide chromatin interactions and gene regulatory effects are yet to be explored. To examine this, we combined chromatin isolation by RNA purification sequencing (ChIRP-seq) and RNA sequencing (RNA-seq) in the hippocampus from handled control and chronic restraint stress (CRS) rats. ChIRP-seq identified 6,664 uc.104 binding peaks under CRS, including 6,517 enriched and 149 reduced. Many peaks were mapped to intronic and promoter-proximal regions of protein-coding genes. Integration of ChIRP-seq with RNA-seq data revealed 1,839 differentially expressed genes associated with uc.104 binding sites, with 106 high-confidence overlaps. Several genes (Gabra3, Htr7, Irs1, Gpr37, Clu, Hspa1b, Ppp3r2, Nfasc, Pcdhac2, and Cysltr2) identified as regulatory targets of uc.104, have been directly implicated in stress responses, synaptic plasticity, and neuroinflammation. Gene ontology and Synapse GO (SynGO) analyses revealed significant enrichment for processes involving dendritic spine formation, synapse organization, and pre- and postsynaptic signaling. Protein-protein interaction analysis identified hub genes, including EGFR, CDC42, IGF1R, CTNNB1, CALM1, CALM3, POLR2A, MDM2, TBP, and CSNK1E, several of which have been linked to stress-responsive pathways. Together, our findings reveal that uc.104 binding to chromatin near stress- and synapse-related genes may act as a regulator of stress-responsive transcriptional networks in the hippocampus. By linking uc.104 occupancy to stress and synaptic responsive genes, this study highlights uc.104 as a potential mediator of stress-induced hippocampal malfunctions. - Source: PubMed
Publication date: 2026/04/19
Verma Anuj KRoy BhaskarPrall KevinHulwi EllieDwivedi Yogesh - Ubiquitin-specific protease 7 (USP7) is a key member of the deubiquitinating enzyme family. It is abnormally overexpressed in various malignancies, including breast cancer, chronic lymphocytic leukemia, and prostate cancer. By regulating pathways such as the p53-MDM2 signaling axis, USP7 promotes tumorigenesis and progression, making it a highly promising therapeutic target for anticancer treatment. Although multiple USP7 inhibitors have been reported, existing screening and evaluation assays exhibit limitations: the ubiquitin-phospholipase A (Ub-PLA) assay frequently produces false-positive results, while the ubiquitin-rhodamine (Ub-Rho) assay is susceptible to interference from compound autofluorescence. To address this challenge, we developed a fluorescence polarization (FP) assay. This employs a rationally designed strategy that exhibits excellent characteristics, making it a simple-to-operate and cost-effective method, suitable for the evaluation of compound bioactivity against USP7. To further validate the practicality and reliability of this FP assay, we conducted a structure-based drug design campaign involving two rounds of systematic structural optimization, yielding 51 novel derivatives featuring pyrazolo[4,3-d]pyrimidine and piperidol scaffolds. Following FP evaluation and Ub-Rho enzyme activity validation, we performed a comprehensive structure-activity relationship (SAR) analysis. Ultimately, in vitro cellular assays identified three compounds (LC-U7-44, LC-U7-48, and LC-U7-50) that exhibit potent USP7 inhibitory activity alongside favorable cellular anti-proliferative effects. Overall, the established FP assay in this study closes a methodological gap in the evaluation of USP7 inhibitors, and the detailed SAR analysis provides a foundation for the further development of potent USP7 inhibitors. - Source: PubMed
Publication date: 2026/04/17
Chen SijiWang MingchenZeng YasiLi XinyuanZhong HuiLiu YilingTao YunsuYang XuLuo ChengChen ShijieXiong Huan