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
- Primary cardiac angiosarcoma is an extremely rare and aggressive malignancy with a poor prognosis. Herein, we describe a case of left atrial angiosarcoma presenting with acute respiratory failure that required emergency surgical intervention, highlighting the condition's diagnostic and therapeutic challenges. - Source: PubMed
Publication date: 2026/05/02
Tsuji AnnaSuzuki KenjiMaeda MotohiroTachibana TakahiroKodani EitaroMotoda NorioSakamoto Shun-IchiroIshii Yosuke - The E3 ubiquitin ligase MDM2, an important oncogene, is a central negative regulator of p53, yet its extensive intrinsically disordered regions have hindered structural characterization of the full-length protein. Here, we integrate AlphaFold ensemble modeling to sample the conformational landscape with all-atom molecular dynamics simulations to characterize structural stability and construct a comprehensive, dynamic model of full-length MDM2. Our analysis identifies a previously uncharacterized autoinhibitory helix (upstream of the central acidic domain) in MDM2 that dynamically masks the N-terminal p53-binding pocket. The dynamic ensembles reveal a multistep unmasking pathway in which the helix pivots away to expose the buried p53-binding pocket. This is followed by a stabilization mechanism whereby, in the bound complex, the same helix repositions to act as an adaptive clamp, anchoring the docked p53. Our study indicates this dynamic gating apparatus to be evolutionarily conserved among MDM2 homologues. These findings provide an atomic-level framework for understanding how MDM2's intrinsic dynamics regulate p53 recognition and suggest new avenues for therapeutic targeting of the p53-MDM2 axis. - Source: PubMed
Publication date: 2026/05/14
Chaudhary HariomPandey ArchnaChowhan Rimpy Kaur - Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, extramedullary hematopoiesis (particularly symptomatic splenomegaly), constitutional symptoms, progressive cytopenias, and, in a subset of patients, leukemic transformation. The advent of the JAK1/2 inhibitor ruxolitinib has revolutionized the management of MF, substantially improving splenomegaly, symptom burden, and, in some settings, overall survival. However, a substantial percentage of patients fail to achieve sustained benefit, are intolerant, or become refractory; real-world and clinical trial data indicate that approximately half of treated patients discontinue ruxolitinib treatment within 3 years and up to approximately 75% within 5 years, with poor outcomes after discontinuation (median survival in several series is approximately 12-14 months). In recent years, several new small molecules that act beyond the JAK-STAT axis have emerged in clinical development. These include agents targeting telomerase (imetelstat), epigenetic regulation via BET inhibition (pelabresib/CPI-0610), the MDM2-p53 axis (navtemadlin/KRT-232), erythroid maturation and the bone marrow microenvironment (luspatercept), PI3K signaling (parsaclisib), and PIM inhibitors (nuvisertib). Early clinical data show promising results for symptom and splenic control in specific settings and, importantly, suggest potential disease-modifying activity (improvements in marrow fibrosis and molecular responses) for some compounds. This review summarizes the biological rationale, key clinical data (efficacy and safety), ongoing randomized trials, and remaining knowledge gaps for these non-JAK small molecules in MF and offers practical considerations for integrating them into contemporary treatment algorithms. - Source: PubMed
Publication date: 2026/04/25
Abruzzese ElisabettaTrawinska Malgorzata MonikaBernardi SimonaCheccoli AlessandraCanichella Martina - Proteasome inhibitors (PIs) are central to multiple myeloma (MM) therapy; however, resistance remains a major clinical challenge, particularly in relapsed/refractory disease. To identify functional mediators of carfilzomib (CFZ) resistance, we performed complementary gain-of-function CRISPR activation and pharmacological screening approaches. These unbiased strategies converged on the E3 ubiquitin ligase MDM2 as a modulator of PI response. MDM2 transactivation enhanced MM cell survival and accelerated recovery following CFZ exposure, supporting a causal role in proteotoxic stress tolerance. Pharmacologic inhibition of MDM2 with NVP-CGM097 synergized with CFZ across multiple PI-sensitive and PI-resistant MM cell lines, irrespective of status. Mechanistically, MDM2 inhibition induced p21 upregulation, cell-cycle arrest, and reduced c-MYC expression, accompanied by impaired activation of DNA damage response mediators. Genetic silencing of MDM2 phenocopied these effects and increased CFZ sensitivity. Importantly, the combination retained efficacy in MM-stromal co-culture models and in primary patient samples, including cases harboring del(17p), while sparing normal peripheral blood mononuclear cells. Collectively, these findings identify MDM2 as a functional driver of PI resistance and support combined MDM2 and proteasome inhibition as a rational therapeutic strategy in MM, including -deficient contexts. - Source: PubMed
Publication date: 2026/05/01
Labrador MaríaCozzubbo SaraPorro MariangelaCumerlato MichelaBandini CeciliaMereu ElisabettaParadzik TinaDonati BenedettaManicardi VeronicaRonchetti DomenicaD'Agostino MattiaLarocca AlessandraGay FrancescaBruno BenedettoCiarrocchi AlessiaChatr-Aryamontri AndrewNeri AntoninoMorelli EugenioPiva Roberto - Lipoma is a benign tumor of adipose tissue, most often located in the subcutaneous tissue or deep soft tissues. It is usually solitary, slow-growing, and asymptomatic. Giant lipomas (≥10 cm or ≥1 kg) are rare and may cause compression of blood vessels and nerves, restricted mobility, and cosmetic deformity. Genetic predisposition is associated with mutations in genes such as High Mobility Group AT-hook 2 (HMGA2) and Domain-Containing Preferred Translocation Partner in Lipoma (LPP). Diagnosis is based on clinical examination and imaging, including ultrasonography, CT, and, in diagnostically equivocal cases, MRI. Suspicious cases are confirmed by histology to rule out malignant tumors. - Source: PubMed
Auyenov MAimagambetov MDyusupov AKairkhanov EKazangapova AImangazinova SAbdrakhmanov SMasalov AZhumazhanova AAuуenov AAuyenov DBakdauletov R