EWSR1
RNA-binding protein EWS (EWS oncogene) (Ewing sarcoma breakpoint region 1 protein) [EWS]
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Ewing's sarcoma (EWS) is a bone cancer arising predominantly in young children. EWSR1 (Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1) gene is ubiquitously expressed in most cell types, indicating it has diverse roles in various cellular processes and organ development. Recently, several studies have shown that missense mutations of EWSR1 genes are known to be associated with central nervous system disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Otherwise, EWSR1 plays epigenetic roles in gene expression, RNA processing, and cellular signal transduction. Interestingly, EWSR1 controls micro RNA (miRNA) levels via Drosha, leading to autophagy dysfunction and impaired dermal development. Ewsr1 deficiency also leads to premature senescence of blood cells and gamete cells with a high rate of apoptosis due to the abnormal meiosis. Despite these roles of EWSR1 in various cellular functions, the exact mechanisms are not yet understood. In this context, the current review overviews a large body of evidence and discusses on what EWSR1 genetic mutations are associated with brain diseases and on how EWSR1 modulates cellular function via the epigenetic pathway. This will provide a better understanding of bona fide roles of EWSR1 in aging and its association with brain disorders.
MeSH Terms
- Aging
- Animals
- Autophagy
- Brain Diseases
- Epigenesis, Genetic
- Humans
- MicroRNAs
- Mutation
- RNA-Binding Protein EWS
Keywords
- Autophagy
- Brain disorders
- EWSR1
- Epigenetic function
- Genetic mutation
- miRNA
The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has rarely been reported. We identified a novel EWSR1-associated chimeric fusion gene in a patient with acute myeloid leukemia harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation. Total RNA paired-end sequencing identified a novel chimeric fusion gene as EWSR1/ELF5, a member of the E26 transformation-specific transcription factor family. Transduction of EWSR1/ELF5 to NIH3T3 cells induced transformation by attenuating with the p53/p21-dependent pathway. The injection of EWSR1/ELF5-transduced NIH3T3 cells into NSG-SCID mice systematically induced the development of tumors in vivo. These results revealed the oncogenic potency of EWSR1/ELF5.
MeSH Terms
- Animals
- Calmodulin-Binding Proteins
- Cell Line, Transformed
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Child, Preschool
- Chromosome Banding
- DNA-Binding Proteins
- Disease Models, Animal
- Female
- Gene Expression
- Gene Expression Profiling
- Humans
- In Situ Hybridization, Fluorescence
- Leukemia, Myeloid, Acute
- Male
- Mice
- Mutation
- NIH 3T3 Cells
- Oncogene Proteins, Fusion
- Proto-Oncogene Proteins c-ets
- Proto-Oncogene Proteins p21(ras)
- RNA-Binding Protein EWS
- RNA-Binding Proteins
- Signal Transduction
- Transcription Factors
- Transcriptome
- Tumor Suppressor Protein p53
Keywords
- Acute myelogenous leukemia
- ELF5
- EWSR1
- TP53
- senescence