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[MED15-TFE3 renal cell carcinoma: a clinicopathological and molecular analysis].
Zhonghua Bing Li Xue Za Zhi
January 2025
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing210002, China.
To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC). A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.
View Article and Find Full Text PDFThe Role of Med15 Sequence Features in Transcription Factor Interactions.
Mol Cell Biol
December 2024
Department of Biology, University of Iowa, Iowa City, Iowa, USA.
Med15 is a general transcriptional regulator and tail module subunit within the RNA Pol II mediator complex. The Med15 protein has a well-structured N-terminal KIX domain, three activator binding domains (ABDs) and several naturally variable polyglutamine (poly-Q) tracts (Q1, Q2, Q3) embedded in an intrinsically disordered central region, and a C-terminal mediator association domain (MAD). We investigated how the presence of ABDs and changes in length and composition of poly-Q tracts influences Med15 activity using phenotypic, gene expression, transcription factor interaction and phase separation assays of truncation, deletion, and synthetic alleles.
View Article and Find Full Text PDFReconciling competing models on the roles of condensates and soluble complexes in transcription factor function.
bioRxiv
November 2024
Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Phase separation explains the exquisite spatial and temporal regulation of many biological processes, but the role of transcription factor-mediated condensates in gene regulation is contentious, requiring head-to-head comparison of competing models. Here, we focused on the prototypical yeast transcription factor Gcn4 and assessed two models for gene transcription activation, i.e.
View Article and Find Full Text PDFTranscriptional coactivator MED15 is required for beta cell maturation.
Nat Commun
October 2024
Diabetes Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.
Article Synopsis
- * Research shows decreased MED15 levels in pancreatic islets from individuals with type 2 diabetes, suggesting its importance in maintaining β-cell function and health.
- * Studies indicate that Med15 interacts with transcription factors Nkx6-1 and NeuroD1 to regulate genes crucial for β-cell maturation, and this is also seen in genetically modified human stem cells that show improved maturation when MED15 levels are increased.
Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.
Open Biol
October 2024
Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary.
Article Synopsis
- The ERM protein family, including Moesin, plays crucial roles in cellular activities, traditionally known for their functions in the cytoplasm, but they've also been implicated in nuclear processes.
- The study identified that Moesin directly interacts with the Mediator complex, specifically its Med15 subunit, and that both proteins are essential for proper gene expression related to heat shock response.
- Moesin, Med15, and heat shock factor (Hsf) form a nuclear complex that includes the monomeric form of actin, providing insight into the mechanisms by which ERM proteins function in the nucleus and highlighting the evolutionary importance of this interaction.
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